Quality assessment of Clinical Practice Guidelines (CPG) for the diagnosis and treatment of inflammatory bowel disease using the AGREE II instrument: a systematic review.

BACKGROUND: The incidence and diagnosis of inflammatory bowel disease (IBD) has increased considerably in recent years. Many clinical practice guidelines (CPG) have been developed for the management of this disease across different clinical contexts, however, little evidence exists on their methodological quality. Therefore, we aimed to systematically evaluate the quality of CPGs for the diagnosis and treatment of IBD using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. METHODS: We identified CPGs by searching databases (MEDLINE - PubMed, EMBASE, CINAHL, LILACS) and other sources of gray literature on January 2022. We included guidelines with specific recommendations for the diagnosis and treatment of IBD and evaluated them with the AGREE II instrument to assess their methodological quality. Six independent reviewers assessed the quality of the guidelines and resolved conflicts by consensus. We assessed the degree of agreement using the intraclass correlation coefficient (ICC) and change in quality over time was appraised in two periods: from 2012 to 2017 and from 2018 to 2022. RESULTS: We analyzed and evaluated 26 CPGs that met the inclusion criteria. The overall agreement among reviewers was moderate (ICC: 0.74; 95% CI 0.36 - 0.89). The mean scores of the AGREE II domains were: "Scope and purpose" 84.51%, "Stakeholder involvement" 60.90%, "Rigor of development" 69.95%, "Clarity of presentation" 85.58%, "Applicability" 26.60%, and "Editorial independence" 62.02%. No changes in quality were found over time. CONCLUSIONS: The quality of the CPGs evaluated was generally good, with a large majority of the assessed guidelines being "recommended" and "recommended with modifications"; despite this, there is still room for improvement, especially in terms of stakeholder involvement and applicability. Efforts to develop high quality CPGs for IBD need to be further optimized.

Grape pomace polyphenols improve insulin response to a standard meal in healthy individuals: A pilot study.

BACKGROUND & AIMS: Dietary polyphenols have beneficial effects on glucose/lipid metabolism in subjects at high risk to develop type 2 diabetes; however, the underlying mechanisms are not clear. We aimed to evaluate: 1) the acute effects of the consumption of a drink rich in polyphenols from red grape pomace (RGPD) on glucose/insulin and triglyceride responses to a standard meal in healthy individuals, and, 2) the relationship between plasma levels of phenolic metabolites and metabolic parameters. METHODS: Twelve healthy men, aged 20-40 years participated in a randomized, controlled study according to a cross-over design. After a 3-day low-polyphenol diet, all participants consumed, on two different days and separated by a one week interval, after an overnight fast, a drink rich in polyphenols (1.562 g gallic acid equivalents (GAE)) or a control drink (CD, no polyphenols), followed after 3 h by a standard meal (960 kcal, 18% protein, 30% fat, 52% CHO). Blood samples were taken at fasting, 3 h after the drink, over 5 h after the standard meal and at fasting on the next day to measure plasma concentrations of glucose, insulin, triglyceride and phenolic metabolites. RESULTS: Glycemic and triglyceride post-meal responses were similar after both the RGPD and the control drink. In contrast, postprandial insulin incremental area (iAUC0-5h) was 31% lower (p < 0.05), insulin secretion index was 18% lower (p < 0.016) and insulin sensitivity (SI) index was 36% higher (p = 0.037) after the RGPD compared to CD. Among phenolic metabolites, gallic acid correlated inversely with the insulin response (r = -0.604; p = 0.032) and positively with the SI index (r = 0.588, p = 0.037). CONCLUSIONS: RGPD consumption acutely reduced postprandial insulin levels and improved insulin sensitivity. This effect could be likely related to the increase in gallic acid levels. This drink, added to usual diet, could contribute to increase the daily intake of polyphenols, with potential health benefits. CLINICALTRIALS. GOV IDENTIFIER: NCT02865278.

Brassica foods as a dietary source of vitamin C: a review.

Brassica genus includes known horticultural vegetables with major economical importance worldwide, and involves vegetables of economical importance being part of the diet and source of oils for industry in many countries. Brassicales own a broad array of health-promoting compounds, emphasized as healthy rich sources of vitamin C. The adequate management of pre- and postharvest factors including crop varieties, growth conditions, harvesting, handling, storage, and final consumer operations would lead to increase or preserve of the vitamin C content or reduced losses by interfering in the catalysis mechanisms that remains largely unknown, and should be reviewed. Likewise, the importance of the food matrix on the absorption and metabolism of vitamin C is closely related to the range of the health benefits attributed to its intake. However, less beneficial effects were derived when purified compounds were administered in comparison to the ingestion of horticultural products such as Brassicas, which entail a closely relation between this food matrix and the bioavailability of its content in vitamin C. This fact should be here also discussed. These vegetables of immature flowers or leaves are used as food stuffs all over the world and represent a considerable part of both western and non-Western diets, being inexpensive crops widely spread and reachable to all social levels, constituting an important source of dietary vitamin C, which may work synergistically with the wealth of bioactive compounds present in these foods.

[Risk of osteoporotic fracture and hip fracture in patients with chronic obstructive pulmonary disease]. / Riesgo de fractura osteoporótica y de cadera en pacientes con enfermedad pulmonar obstructiva crónica.

AIM: Osteoporosis is a frequent comorbidity in patients with chronic obstructive pulmonary disease (COPD). We have studied the risk of major osteoporotic fracture and hip fracture in patients with COPD. PATIENTS AND METHODS: A multicenter cross-sectional study was performed in Spain in 26 hospitals of 16 regional communities. Patients diagnosed with COPD who required admission to the Internal Medicine Service due to exacerbation of their respiratory disease were enrolled. COPD was confirmed by post-bronchodilator spirometry in stable state: maximum expiratory volume in the first second (FEV1) < 80% of the theoretical value and quotient FEV(1)/FVC < 0.70 and percent predicted after the administration of a bronchodilator. Dyspnea was evaluated with the modified Medical Research Council (mMRC) dyspnea scale. The principal variable was the likelihood of fracture evaluated with the FRAX® tool for the Spanish population. RESULTS: Three hundred and ninety two patients, 347 (88%) men, with a mean (SD) age of 73.7 (8.9) years and a mean FEV1 of 1.23 liters (43.3% of predicted) were enrolled. Only 37 patients (9.4%), 27 men and 10 women had been diagnosed previously of osteoporosis. Overall, 1.8% (95% CI: 0.9-3.6) had a 10-year probability of major osteoporotic fracture ≥ 20% and 49.7% (95% CI: 44.8-54.7) had a probability of hip fracture ≥ 3%. No relationship was observed between the probability of fracture and GOLD stage or mMRC dyspnea scale. CONCLUSIONS: The diagnosis of osteoporosis is uncommon in our COPD patients. However, half of them have a high probability of a hip fracture in the next 10 years.

Tratamiento quirúrgico de la inestabilidad rotuliana recurrente con reconstrucción del ligamento patelofemoral medial usando autoinjerto semitendinoso / Surgical treatment of recurrent patellar instability with medial patellofemoral ligament reconstruction using semitendinosus tendon autograft

The medial patellofemoral ligament (MPFL) reconstruction is an option for the recurrent patellar instability. We developed a prospective study whose objective was to show the functional results at 6 and 12 months of patients who underwent MPFL reconstruction with semitendinosus (St) autograft. Four patients (5 knees) were treated between May 2006 and May 2008. The Kujala´s test before surgery in all patients was poor (< 50 points); 6 months after the surgery 4 cases turned out to be "good and very good" (only 1 case "poor", but increased her score to 78 points) and after 12 months of follow-up, 5 cases scored "very good and excellent" (score > 90 points). The Tegner´s test showed an increased of activity that was normal for the patients, and with the Insall´s test all patients referred very satisfied 12 months after surgery. Up to this stage, there has been no recurrence. In our local environment, the MPFL reconstruction with St. is a valid treatment to recover the patellofemoral mecanic.

La reconstrucción del ligamento patelofemoral medial (LPFM) es una alternativa en la inestabilidad rotuliana recurrente. Desarrollamos un estudio prospectivo con el objetivo de exponer los resultados funcionales a los 6 y 12 meses de pacientes sometidos a una reconstrucción del LPFM con semitendinoso (St). Son 4 pacientes (5 rodillas) operados entre mayo 2006 y mayo 2008. El test de kujala preoperatorio era "malo" (< 50 pts) en todos, a los 6 meses post op. 4 casos de "bueno y muy bueno" resultado (sólo 1 caso "malo", pero con incremento de su score a 78) y a los 12 meses (5 casos) todos con función "muy bueno y excelente" (score > 90 pts). El test de Tegner mostró un aumento del nivel de actividad considerada de normal en todos los pacientes, y en el test de Insall todos refieren excelente mejoría a los 12 meses. Hasta la fecha no existen recidivas. En nuestro medio local, la reconstrucción del LPFM con St. es una alternativa válida para recuperar la mecánica patelofemoral.

Expansion of formalin-evoked Fos-immunoreactivity in rats with a spinal cord injury.

Peripheral tissue injury as well as spinal cord injury (SCI) may lead to sensitization of dorsal horn neurons and alterations in nociceptive processing. Thus, peripheral injuries experienced by SCI patients, even if not initially perceived, could result in a persistent and widespread activation of dorsal horn neurons and emerge as chronic pain with interventive repair or modest recovery from SCI. To visualize the spinal neuron response to peripheral tissue injury following complete SCI in rats, the neural transcription factor Fos was quantitated in the spinal cord. Two weeks following either a complete transection of the spinal cord at the level of T8 or a sham surgery (laminectomy), rats were injected with formalin into the left hind paw. Sham-operated rats demonstrated biphasic hind paw pain-related behavior following formalin injection, but transected rats displayed fewer behaviors in the second (tonic) phase. Stereological analysis of the sham group revealed that the extent of formalin-induced Fos expression was within the lumbar dorsal horn, with numerous Fos-like immunoreactive profiles in the ipsilateral dorsal horn and some contralateral immunoreactive profiles. In contrast, the level of Fos-like immunoreactivity in the transected group was significantly elevated and expanded in range compared to the sham group, with increases observed in the normal laminar distribution regions, as well as multi-segmentally through sacral levels and increases in the contralateral dorsal horn segments. The data demonstrate that widespread activation of spinal, especially dorsal horn, neurons following peripheral insult can occur in the injured spinal cord, despite reduced pain responsiveness, and suggests that exaggerated pain may emerge as spinal recovery or repair progresses.

MIF loss impairs Myc-induced lymphomagenesis.

Macrophage migration inhibitory factor (MIF) is a potent regulator of inflammation and cell growth. Using the Emu-Myc lymphoma mouse model, we demonstrate that loss of MIF markedly delays the onset of B-cell lymphoma development in vivo. The molecular basis for this MIF-loss-induced phenotype is the perturbed DNA-binding activity of E2F factors and the concomitantly enhanced tumor suppressor activity of the p53 pathway. Accordingly, premalignant MIF-null Emu-Myc B-cells are predisposed to delayed S-phase progression and increased apoptosis. MIF-deficient lymphomas that do arise under these conditions contain frequent ARF deletions and p53 inactivating mutations. Conversely, MIF expression is retained in tumors developed by wild-type Emu-Myc animals, and the presence of one or both MIF alleles is sufficient to accelerate the development of Myc-induced lymphomas. Collectively, these results indicate that MIF promotes Myc-mediated tumorigenesis, at least in the B-lymphoid compartment, and implicate MIF as a mediator of malignant cell growth in vivo.

Changes in the sympathetic skin response after thoracoscopic sympathectomy in patients with primary palmar hyperhidrosis.

OBJECTIVE: To investigate whether thoracic sympathectomy induced any change in the pattern of abnormalities or in the waveform of the sudomotor skin response (SSR) in patients with primary palmar hyperhidrosis (PPH). METHODS: We recorded the SSR to median nerve electrical stimuli before and after bilateral thoracoscopic sympathectomy in 27 patients with PPH. We analyzed the changes in amplitude, type of waveform and pattern of abnormality. RESULTS: All patients reported symptomatic improvement. The amplitude of the SSR decreased significantly in patients examined within 1 year after surgery, but was not different in patients examined after 1 year. The number of abnormally enhanced responses reduced after surgery, but there was no significant change in the number of patients with enhanced excitability recovery or with double-peak responses to single stimuli. There was a significant increase in the number of SSRs with a predominantly negative waveform after surgery. CONCLUSIONS: The persistence of SSR abnormalities after surgery suggests that the central nervous system dysfunction is not modified by sympathectomy. The change of the waveform to predominantly negative type after surgery could be the consequence of the decrease in the production of sweating. SIGNIFICANCE: Our results show the effects of sympathectomy on the SSR and on its abnormal patterns in patients with PPH.

Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial.

OBJECTIVES: A randomized, masked, controlled trial was conducted to assess effects of supplementing premature infant formulas with oils containing the long-chain polyunsaturated fatty acids, arachidonic acid (AA; 20:4 n6), and docosahexaenoic acid (DHA; 22:6 n3) on growth, visual acuity, and multiple indices of development. METHODS: Infants (N = 470) with birth weights 750 to 1800 g were assigned within 72 hours of the first enteral feeding to 1 of 3 formula groups with or without long-chain polyunsaturated fatty acids: 1) control (N = 144), 2) AA+DHA from fish/fungal oil (N = 140), and 3) AA+DHA from egg-derived triglyceride (egg-TG)/fish oil (N = 143). Infants were fed human milk and/or Similac Special Care with or without 0.42% AA and 0.26% DHA to term corrected age (CA), then fed human milk or NeoSure with or without 0.42% AA and 0.16% DHA to 12 months' CA. Infants fed exclusively human milk to term CA (EHM-T; N = 43) served as a reference. RESULTS: Visual acuity measured by acuity cards at 2, 4, and 6 months' CA was not different among groups. Visual acuity measured by swept-parameter visual-evoked potentials in a subgroup from 3 sites (45 control, 50 AA+DHA [fish/fungal]; 39 AA+DHA [egg-TG/fish]; and 23 EHM-T) was better in both the AA+DHA (fish/fungal; least square [LS] means [cycle/degree] +/- standard error [SE; octaves] 11.4 +/- 0.1) and AA+DHA (egg-TG/fish; 12.5 +/- 0.1) than control (8.4 +/- 0.1) and closer to that of the EHM-T group (16.0 +/- 0.2) at 6 months' CA. Visual acuity improved from 4 to 6 months' CA in all but the control group. Scores on the Fagan test of novelty preference were greater in AA+DHA (egg-TG/fish; LS means +/- SE, 59.4 +/- 7.7) than AA+DHA (fish/fungal; 57.0 +/- 7.5) and control (57.5 +/- 7.4) at 6 months' CA, but not at 9 months' CA. There were no differences in the Bayley Mental Development Index at 12 months' CA. However, the Bayley motor development index was higher for AA+DHA (fish/fungal; LS means +/- SE, 90.6 +/- 4.4) than control (81.8 +/- 4.3) for infants

Insulin homeostasis in the extremely low birth weight infant.

The need to improve the nutritional status of extremely low birth weight infants has resulted in a higher incidence of problems related to glucose intolerance. The inability of the newborn to inhibit gluconeogenesis in response to a glucose infusion has been postulated as an important determinant of the hyperglycemia observed in extremely low birth weight infants. The 2 proposed mechanisms to explain this finding include inappropriate secretion of insulin by the pancreas and decrease sensitivity of the liver to the gluco-regulatory effect of insulin. The capacity of extremely low birth weight infants to oxidize glucose at higher rates, and the positive effect that insulin may have in glucose utilization and tolerance, support the use of insulin in the prevention and treatment of hyperglycemia. Continuous infusion of insulin appears to be safe for the treatment of hyperglycemia, based on the available studies. However, the effectiveness of insulin treatment needs to be critically tested further before it can be implemented in routine clinical practice.

Essential fatty acids in early life: structural and functional role.

Essential fatty acids (EFA) are structural components of all tissues and are indispensable for cell membrane synthesis; the brain, retina and other neural tissues are particularly rich in long-chain polyunsaturated fatty acids (LCPUFA). These fatty acids serve as specific precursors for eicosanoids that regulate numerous cell and organ functions. Results from animal and recent human studies support the essential nature of n-3 EFA in addition to the well-established role of n-6 EFA for human subjects, particularly in early life. The most significant effects relate to neural development and maturation of sensory systems. Recent studies using stable-isotope-labelled tracers demonstrate that even preterm infants are able to form arachidonic acid (AA) and docosahexaenoic acid (DHA), but that synthesis is extremely low. Intracellular fatty acids or their metabolites regulate transcriptional activation of gene expression during adipocyte differentiation, and retinal and nervous system development. Regulation of gene expression by LCPUFA occurs at the transcriptional level and is mediated by nuclear transcription factors activated by fatty acids. These nuclear receptors are part of the steroid hormone receptor family. Two types of polyunsaturated fatty acid responsive transcription factors have been characterized, the peroxisome proliferator-activated receptor (PPAR) and the hepatic nuclear factor 4alpha. DHA also has significant effects on photoreceptor membranes involved in the signal transduction process, rhodopsin activation, and rod and cone development. Comprehensive clinical studies have shown that dietary supplementation with marine oil or single-cell oils, sources of LCPUFA, results in increased blood levels of DHA and AA, as well as an associated improvement in visual function in formula-fed premature infants to match that of human milk-fed infant. Recent clinical trials convincingly support LCPUFA supplementation of preterm infant formulations and possibly term formula to mimic human milk composition.

Essential fatty acid metabolism in the micropremie.

Lipids are structural components of all tissues and are indispensable for cell membrane synthesis. The brain, retina, and other neural tissues are particularly rich in LCPUFAs, affecting neural structural development and function. LCPUFAs serve also as specific precursors for eicosanoid production (prostaglandins, prostacyclins, thromboxanes, and leukotrienes). These autocrine and paracrine mediators are powerful regulators of numerous cell and tissue functions (e.g., thrombocyte aggregation, inflammatory reactions, and leukocyte functions, vasoconstriction and vasodilatation, blood pressure, bronchial constriction, uterine contraction). Dietary lipid intake affects cholesterol metabolism at an early age and is associated with cardiovascular morbidity and mortality in later life. Over recent years, the role of fatty acids in modulating signal transduction and regulating gene expression have been described, emphasizing the complex of fatty acid effects. Dietary fatty acids, especially LCPUFA, can have significant effects in the modulation of developmental processes affecting the clinical outcomes of extremely premature infants.

Long chain polyunsaturated fatty acid formation in neonates: effect of gestational age and intrauterine growth.

The present study was designed to evaluate the effect of gestational age and intrauterine growth on the long chain polyunsaturated fatty acid (LCP) synthesis from dietary precursors in neonates as reflected by plasma pools. These have been considered conditionally essential nutrients for normal growth, sensory maturation, and neurodevelopment. In vivo elongation/desaturation of deuterated d5-linoleic acid (d5-LA) to form arachidonic acid (AA), and d5-alpha-linolenic acid (d5-LNA) to form docosahexaenoic acid (DHA), was studied in 19 preterm appropriate-for-gestational-age (AGA) infants, 11 AGA term, and 11 intrauterine growth-retarded (IUGR) infants. They received a dose of 50 mg/kg body weight of d5-LA and d5-LNA enterally during the first days of life; d5-labeled derivatized fatty acids were determined in blood samples obtained at 24, 48, and 96 h after dosing. Lipids were extracted and fatty acids analyzed by gas chromatography and negative ion mass spectrometry. Mean concentrations, microg/mL, and d5/d0 for n-3 and n-6 precursor and products were computed at various times and were also integrated over the complete study period. Significantly higher time-integrated concentration of d5-AA and d5-DHA were observed in preterm infants relative to the other two groups. Time-integrated enrichment of DHA relative to LNA was 100-fold lower in preterms, 410-fold lower in term, and 27-fold lower in IUGR infants. Similar significant declines in product to precursor enrichments were noted for the n-6 series. A significant negative correlation of AA and DHA formation based on time-integrated d5/d0 ratios with gestational age was noted; product/ precursor enrichment versus gas chromatography for the n-6 series had an r of -0.5, p = 0.001, and for the n-3 series had an r of -0.6, p = 0.0001. Birth weight or weight adequacy did not add further strength to the relationship. We conclude that LCP formation from deuterated precursors occurs as early as 26 wk gestation, and in fact is more active at earlier gestational ages; growth retardation appears to slow down or diminish LCP formation. No quantitative estimates of LCP synthesis or nutritional sufficiency can be derived from these data.