Protocol For Patients With Suspected Acute Porphyria. / Protocolo de actuación en pacientes con sospecha de porfiria aguda.

Porphyrias are a group of congenital errors in porphyrin metabolism and in the heme biosynthetic pathway. Accumulation of porphyrin precursors (delta-aminolaevulinic acid and porphobilinogen) is responsible for the neurovisceral crises of acute porphyria, which, when expressed clinically, start with intense abdominal pain. During crises, the urinary elimination of porphobilinogen and delta-aminolaevulinic acid is always very high. Excessive porphobilinogen concentration in urine is easily identified using the simple Hoesch test. A negative test rules out a current porphyric crisis. The clinical protocol for patients with acute abdominal pain of unknown origin in whom a positive Hoesch test leads to the suspicion of acute porphyria is based on the following aspects: initial clinical assessment in the emergency department, suppression of potential triggers, specific treatment for the crisis with hemin and/or glucose overload and symptomatic treatment.

Extracolonic Cancer in Inflammatory Bowel Disease: Data from the GETECCU Eneida Registry.

OBJECTIVES: The objective of this study was (a) To know the prevalence and distribution of extracolonic cancer (EC) in patients with inflammatory bowel disease (IBD); (b) To estimate the incidence rate of EC; (c) To evaluate the association between EC and treatment with immunosuppressants and anti-tumor necrosis factor (TNF) agents. METHODS: This was an observational cohort study. INCLUSION CRITERIA: IBD and inclusion in the ENEIDA Project (a prospectively maintained registry) from GETECCU. EXCLUSION CRITERIA: Patients with EC before the diagnosis of IBD, lack of relevant data for this study, and previous treatment with immunosuppressants other than corticosteroids, thiopurines, methotrexate, or anti-TNF agents. The Kaplan-Meier method was used to evaluate the impact of several variables on the risk of EC, and any differences between survival curves were evaluated using the log-rank test. Stepwise multivariate Cox regression analysis was used to investigate factors potentially associated with the development of EC, including drugs for the treatment of IBD, during follow-up. RESULTS: A total of 11,011 patients met the inclusion criteria and were followed for a median of 98 months. Forty-eight percent of patients (5,303) had been exposed to immunosuppressants or anti-TNF drugs, 45.8% had been exposed to thiopurines, 4.7% to methotrexate, and 21.6% to anti-TNF drugs. The prevalence of EC was 3.6%. In the multivariate analysis, age (HR=1.05, 95% CI=1.04-1.06) and having smoked (hazards ratio (HR)=1.47, 95% confidence interval (CI)=1.10-1.80) were the only variables associated with a higher risk of EC. CONCLUSIONS: Neither immunosuppressants nor anti-TNF drugs seem to increase the risk of EC. Older age and smoking were associated with a higher prevalence of EC.

Volume integrated phase modulator based on funnel waveguides for reconfigurable miniaturized optical circuits.

We demonstrate the integration of a miniaturized 30(x) µm×30(y) µm×2.7(z) mm electro-optic phase modulator operating in the near-IR (λ=980 nm) based on the electro-activation of a funnel waveguide inside a paraelectric sample of photorefractive potassium lithium tantalate niobate. The modulator forms a basic tassel in the realization of miniaturized reconfigurable optical circuits embedded in a single solid-state three-dimensional chip.

UNITY: A low-field magnetic resonance neuroimaging initiative to characterize neurodevelopment in low and middle-income settings.

Measures of physical growth, such as weight and height have long been the predominant outcomes for monitoring child health and evaluating interventional outcomes in public health studies, including those that may impact neurodevelopment. While physical growth generally reflects overall health and nutritional status, it lacks sensitivity and specificity to brain growth and developing cognitive skills and abilities. Psychometric tools, e.g., the Bayley Scales of Infant and Toddler Development, may afford more direct assessment of cognitive development but they require language translation, cultural adaptation, and population norming. Further, they are not always reliable predictors of future outcomes when assessed within the first 12-18 months of a child's life. Neuroimaging may provide more objective, sensitive, and predictive measures of neurodevelopment but tools such as magnetic resonance (MR) imaging are not readily available in many low and middle-income countries (LMICs). MRI systems that operate at lower magnetic fields (< 100mT) may offer increased accessibility, but their use for global health studies remains nascent. The UNITY project is envisaged as a global partnership to advance neuroimaging in global health studies. Here we describe the UNITY project, its goals, methods, operating procedures, and expected outcomes in characterizing neurodevelopment in sub-Saharan Africa and South Asia.

Time of the day of exercise impact on cardiovascular disease risk factors in adults: a systematic review and meta-analysis.

OBJECTIVES: To compare the effect of a single bout of morning vs. evening exercise on cardiovascular risk factors in adults. DESIGN: Systematic review and meta-analysis. METHODS: A systematic search of studies was conducted using PubMed and Web of Science from inception to June 2022. Selected studies accomplished the following criteria: crossover design, acute effect of exercise, blood pressure, blood glucose, and/or blood lipids as the study's endpoint, a washout period of at least 24 h, and adults. Meta-analysis was performed by analyzing: 1) separated effect of morning and evening exercise (pre vs. post); and 2) comparison between morning and evening exercise. RESULTS: A total of 11 studies were included for systolic and diastolic blood pressure and 10 studies for blood glucose. Meta-analysis revealed no significant difference between morning vs. evening exercise for systolic blood pressure (g ∆ = 0.02), diastolic blood pressure (g ∆ = 0.01), or blood glucose (g ∆ = 0.15). Analysis of moderator variables (age, BMI, sex, health status, intensity and duration of exercise, and hour within the morning or evening) showed no significant morning vs. evening effect. CONCLUSIONS: Overall, we found no influence of the time of the day on the acute effect of exercise on blood pressure neither on blood glucose.

Neurocognitive correlates of the varied domains of outcomes at 20 year follow-up of first-episode psychosis.

Little is known about long-term outcomes of the first episode of psychosis (FEP) other than in the symptomatic domain. We hypothesised that cognitive impairment is associated with poorer multi-domain outcomes at a long-term follow-up of FEP patients. We followed-up 172 FEP patients for a mean of 20.3 years. Ten outcome dimensions were assessed (symptomatic, functional and personal recovery, social disadvantage, physical health, suicide attempts, number of episodes, current drug use, chlorpromazine equivalent doses (CPZ), and schizophrenia/schizoaffective disorder final diagnosis). Cognition was assessed at follow-up. Processing speed and verbal memory deficits showed significant associations with poor outcomes on symptomatic, social functioning, social disadvantage, higher number of episodes, and higher CPZ. Significant associations were found between visual memory impairments were significantly associated with low symptomatic and functional recovery, between attentional deficits and a final diagnosis of schizophrenia/schizoaffective disorder, and between social cognition deficits and poor personal recovery.Lower cognitive global scores were significantly associated with all outcome dimensions except for drug abuse and physical status. Using multiple outcome dimensions allowed for the inclusion of the patients' perspective and other commonly neglected outcome measures. Taken together, cognitive impairment in FEP patients is strongly related to poor performance on several outcome dimensions beyond symptomatic remission.

Adipokine profiles and lipodystrophy in HIV-infected children during the first 4 years on highly active antiretroviral therapy.

OBJECTIVE: The aim of the study was to evaluate the evolution of plasma adipokines and lipodystrophy in protease inhibitor-naive vertically HIV-infected children on highly active antiretroviral therapy(HAART). PATIENTS AND METHODS: We carried out a multicentre retrospective study of 27 children during 48 months on HAART. Every 3 months, CD4+ T-cells, CD8+ T-cells, viral load (VL), cholesterol, triglycerides, lipoproteins and adipokines were measured. Diagnoses of lipodystrophy were based on clinical examinations. RESULTS: We found hypercholesterolaemia (4200 mg/dL) in 9.5, 30.4, 21.7, 14.3 and 13.3% of the subjects at months 0, 12, 24, 36 and 48, respectively, and hypertriglyceridaemia (4170 mg/dL) in 14.3, 8.3, 13,4.5 and 0% at the same time-points. During follow-up, and especially at the end of the study, we found an increase in plasma resistin levels and significant increases in total plasminogen activator inhibitor type 1, adiponectin, and leptin levels (Po0.05). We also observed slight increases in the leptin/adiponectin ratio, homeostatic model assessment, and C-peptide values during the first months of treatment followed by a moderate decrease or stabilization after 24 months on HAART.At the end of the study, 12 of the 27 children (44.4%) had lipodystrophy, 10 (37%) had lipoatrophy,and 11 (40.7%) had lipohypertrophy; and only three of the 27 children (11.1%) were diagnosed with lipoatrophy and lipohypertrophy with scores 2. CONCLUSIONS: HIV-infected children showed an increase in serum adipokine levels, but this was not associated with the emergence of lipodystrophy during 48 months on HAART.

Diagnosis of advanced fibrosis in HIV and hepatitis C virus-coinfected patients via a new noninvasive index: the HGM-3 index.

BACKGROUND: Noninvasive tests are increasingly being used for the assessment of liver fibrosis. We aimed to develop a serum index for the identification of advanced fibrosis (F>or=3) in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: We carried out a cross-sectional study on a group of 195 patients comprised of an estimation group (EG; n=127) and a validation group (VG; n=68) who all underwent liver biopsy and had not received previous interferon therapy. Liver fibrosis was estimated using the METAVIR score. We developed a new serum index (HGM-3) dependent on levels of platelets, alkaline phosphatase, hepatic growth factor, tissue inhibitor of metalloproteinase-1 and hyaluronic acid. RESULTS: In the EG, the area under the receiver operating characteristic curve (AUC-ROC) of HGM-3 for identification of F>or=3 was 0.939 [95% confidence interval (CI) 0.899, 0.979] which was significantly higher than the AUC-ROC of the HGM-2, FIB-4, aspartate aminotransferase to platelet ratio (APRI) and Forns' indexes. With HGM-3 <0.135 for F<3, 57 patients were correctly identified and two patients were misclassified. We found the presence of F<3 with 96.6% certainty. The negative likelihood ratio (LR) was <0.1 and the diagnostic odds ratio (DOR) was >40. With HGM-3 >0.570 in the EG for F>or=3, 31 patients were correctly identified, and five patients were misclassified. We found the presence of F>or=3 with 86.1% certainty. The positive LR was >12 and the DOR was >40. For the VG, the diagnostic accuracy values were similar to the values for the EG. CONCLUSIONS: HGM-3 appears to be an accurate noninvasive method for the diagnosis of bridging fibrosis and cirrhosis in HIV/HCV-coinfected patients.

CD81 expression in peripheral blood lymphocytes before and after treatment with interferon and ribavirin in HIV/HCV coinfected patients.

BACKGROUND: CD81 is expressed on lymphocytes and confers HCV viral infectivity support. The aim of our study was to quantify CD81 expression in peripheral blood B- and T-cells of HCV/HIV-coinfected patients and healthy subjects to examine its association with several HCV virological characteristics and the therapeutic responsiveness to HCV antiviral treatment. METHODS: We carried out a cross-sectional study on 122 naïve patients. For a duration of 48 weeks, 24 out of 122 patients underwent HCV antiviral therapy with interferon (IFN)-alpha and ribavirin. T- and B-cell subsets were analysed by flow cytometry. RESULTS: We found that HIV/HCV coinfected patients with HCV-RNA > or =850 000 IU/mL had lower values of %CD19+CD81-CD62L+ and %CD19+CD62L+; and higher values of CD19+CD81+CD62L- and CD19+CD81+ percentages and absolute counts than patients with HCV-RNA <850 000 IU/mL. Similarly, HIV/HCV coinfected patients with the genotype 1 had lower values of %CD19+CD81-CD62L+ and higher values of CD3+CD81+CD62L- and CD3+CD81+ percentages and absolute counts than patients without genotype 1. Moreover, we found that HIV/HCV coinfected patients had higher values of %CD19+HLA-DR+CD25+, %CD19+CD40+CD25+ and %CD19+CD25+ than healthy control patients. When we studied the B- and T-cell subset kinetics of 24 HIV/HCV coinfected patients on HCV antiviral therapy, we found a significant decrease in CD3+CD81+and CD3+CD81+CD62L- subsets and a significant increase in CD3+CD62L+ and CD3+CD81+CD62L+ percentages and absolute counts, but the variation in these markers disappeared several months after stopping the treatment. CONCLUSIONS: We observed a different pattern of CD81 T-cell and B-cell levels in naïve HIV/HCV coinfected patients according to HCV virological status and their subsequent variations during HCV antiviral treatment. CD81 expression might influence HCV pathogenesis and response to HCV antiviral treatment.

Plasma homocysteine levels are associated with ulceration of the foot in patients with type 2 diabetes mellitus.

BACKGROUND: To examine the association of biochemical markers of risk (plasma Hcy, microalbuminuria, lipoprotein (a)(Lp(a)) and diabetic dyslipidaemia) with the prevalence of diabetic foot ulceration in type 2 diabetic patients. METHODS: Case/control study conducted in 198 type 2 diabetic patients. 89 patients have foot ulcers and 109 have no foot ulcers (control group), in order to establish ORs for diabetic foot ulceration. In all subjects plasma Hcy, Lp(a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, HbA(1c) and microalbuminuria were measured using standard procedures. RESULTS: Plasma Hcy, microalbuminuria, HbA(1c) and apolipoprotein B levels were significantly higher in patients with foot ulceration compared with the control group. Plasma lipids, Lp(a), vitamin B12 and folic acid values were similar in both groups. In the logistic regression model, plasma Hcy (OR 1.09; 95% CI 1.04-1.69), microalbuminuria (OR 1,01; 95% CI 1.01-1.17) and HbA(1c) levels (OR 1.33; 95% CI 1.04-1.69) were independent risk factors for the presence of diabetic foot ulceration. CONCLUSIONS: In our study, for each micromol increase in plasma Hcy levels there was a 10% increase in the risk of diabetic foot ulceration. In addition, plasma homocysteine, HbA(1c) and microalbuminuria accounted for 50% prevalence risk of diabetic foot ulceration. Further prospective studies should be conducted to confirm the association of plasma Hcy levels with the risk of foot ulceration.

Serum levels of fibrosis biomarkers measured early after liver transplantation are associated with severe hepatitis C virus recurrence.

This prospective study analyzed the relationship between several biological markers related to liver fibrosis at 3 months and 1 year post liver transplantation in 37 patients (19 with hepatitis C virus [HCV], 18 with alcoholic liver disease). Severe HCV recurrence (HCV-SR) was defined as fibrosis stage > or =F1 (METAVIR score) at 1 year and/or a value of hepatic venous pressure gradient > or=6 mmHg. We found HCV-SR patients had higher values of monocyte chemotactic protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and hyaluronic acid (HA) than non-severe HCV recurrence patients (P<0.05). Moreover, receiver operating characteristic curve analysis showed that interferon-inducible protein 10 (IP-10) (area under the curve [AUC]: 0.74; confidence interval [CI] 95%: 0.49-0.91; P=0.043), MCP-1 (AUC: 0.78; CI 95%: 0.54-0.94; P=0.007), sVCAM-1 (AUC: 0.89; CI 95%: 0.67-0.98; P=0.005), and HA (AUC: 0.80; CI 95%: 0.55-0.94; P=0.035) have good predictive capacity for identifying severe HCV infection. The evaluation of these biomarkers may be useful in the early identification of patients in whom a more aggressive therapeutic approach could be necessary.

Viral kinetics during the first month of treatment in patients with genotype 1 chronic hepatitis C.

OBJECTIVE: to identify predictive factors of response to pegylated interferon alpha-2b and ribavirin in patients with genotype 1 chronic hepatitis C. Viral kinetics were studied in weeks 2 and 4. METHODS: a prospective and consecutive study of patients with genotype 1 chronic hepatitis C referred to our Hepatology Clinic between January 2004 and October 2006 for antiviral treatment. Baseline data were recorded and viremia levels were determined hours before the weekly dose of pegylated interferon by qualitative and quantitative PCR. RESULTS: 57 patients were included in the study, although 3 of these were excluded during follow up; 65% were male (n = 35), with a mean age of 42 (26-65) years. Baseline viremia levels were > 800,000 IU/mL in 67% (n = 36). Liver biopsy was performed in 86% (n = 46), 22% (n = 12) had advanced fibrosis. Forty were naïve, 4 relapsing and 10 non-responders. Ribavirin dose was modified in one patient alone due to adverse effects. End treatment response and sustained virological response (SVR) were 59 and 41%, respectively. A univariate analysis revealed a statistically significant association of SVR with baseline viremia (p = 0.006), baseline GGT (p = 0.025), and a reduction in viremia > or =2 logs at 2, 4 and 12 weeks (p = 0.001). The extent of viremia reduction at week 2 was associated with 100% SVR, and at 4 weeks the positive predictive values was 84% and the negative predictive values was 96.5%. A subanalysis of the naïve group yielded analogous results. CONCLUSIONS: in our study, a reduction in viremia > or = 2 logs 2 weeks after treatment could ensure SVR. At 4 weeks, most non-responders could be identified.

Endoscopic follow-up of gastric ulcer in a population at intermediate risk for gastric cancer.

OBJECTIVES: Primary: to assess the necessity of a second endoscopy with a pathology study to confirm the healing of all gastric ulcers previously diagnosed through endoscopy in a population at intermediate risk for gastric cancer. Secondary: to assess correlation between endoscopic findings and pathology diagnosis. PATIENTS AND METHODS: a prospective analysis of patients diagnosed with gastric ulcer through endoscopy at Hospital General de Ciudad Real (Spain) over three years. We collected demographic, clinical, endoscopic, and pathological data for the first and subsequent endoscopies. We collected at least six biopsies obtained from ulcer margins, and assessed H. pylori infection. RESULTS: Three hundred and two patients were included in this study. H. pylori infection was diagnosed in 173 (57%), and 113 (37%) patients had used NSAIDs. The positive and negative predictive value for malignancy of endoscopic diagnosis regarding ulcer fold, base, and margins were 34 and 97%, respectively. Only one patient was diagnosed with a tumor during the second endoscopy. At the end of follow-up, the etiology of the ulcer was considered as peptic in 276 patients; Crohn s disease-related in one, and neoplastic in 25 patients (21 adenocarcinomas, 4 lymphomas). CONCLUSIONS: in an intermediate-risk population for gastric cancer a second endoscopy is not justified for gastric ulcer patients when endoscopy and biopsy results do not suggest malignancy.

Effectiveness and Safety of the Switch from Remicade® to CT-P13 in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: To evaluate the clinical outcomes in patients with IBD after switching from Remicade® to CT-P13 in comparison with patients who maintain Remicade®. METHODS: Patients under Remicade® who were in clinical remission with standard dosage at study entry were included. The 'switch cohort' [SC] comprised patients who made the switch from Remicade® to CT-P13, and the 'non-switch' cohort [NC] patients remained under Remicade®. RESULTS: A total of 476 patients were included: 199 [42%] in the SC and 277 [58%] in the NC. The median follow-up was 18 months in the SC and 23 months in the NC [p < 0.01]. Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR = 3.5, 95% confidence interval [CI] = 2-6). Thirteen percent of patients had adverse events in the NC, compared with 6% in the SC [p < 0.05]. CONCLUSIONS: Switching from Remicade® to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. The nocebo effect might have influenced this result. Switching from Remicade® to CT-P13 was safe.

[Difficult treatment of amiodarone-induced thyrotoxicosis: a case report]. / Dificultad en el tratamiento del hipertiroidismo por amiodarona. Presentación de un caso.

Amiodarone causes changes in thyroid function tests in about 15-20% of patients, inducing either hypothyroidism or thyrotoxicosis. The iodine load and the destructive thyroiditis caused by amiodarone produce thyrotoxicosis. We report a case of amiodarone-induced thyrotoxicosis diagnosed when investigating the reason for worsening of cardiac function. Prognosis and treatment of cardiac disorder were determined by thyrotoxicosis. The management needed a closed monitoring of thyroid function. Treatment was based on high doses of propylthiouracil and dexamethasone, but they couldn t control cardiac condition and surgery was warranted. When amiodarone-induced thyrotoxicosis is refractory to medical treatment, we believe surgery should be considered earlier.

[Use of radioguided surgery in the surgical treatment of osteoid osteoma]. / Uso de la cirugía radiodirigida en el tratamiento quirúrgico del osteoma osteoide.

OBJECTIVE: Osteoid osteoma is the third most common benign bone tumor and complete surgical resection is definitive treatment. There are a limited number of publications on the use of radioguided surgery in this type of lesion. To assess the utility of radioguided surgery in our environment as a method of surgical treatment of this tumor. MATERIAL AND METHODS: We retrospectively evaluated 12 patients (2 women and 10 men, age range 9-44 years) with clinical and radiological suspicion of osteoid osteoma. Bone scintigraphy showed foci of pathology uptake compatible with suspected lesion in the femur (4 cases), tibia (3), vertebral column (3), humerus (1) and talus (1). Subsequently patients underwent surgical treatment by radioguided surgery after injection of a dose of (99m)Tc-hydroxy diphosphonate. The nidus was removed using gamma probe and mini gamma camera, considering the technique to be completed when its counts decreased to the levels of the surrounding bone counts. RESULTS: Lesions were located in all patients (12 of 12), and were confirmed histologically in 8 of them, including an osteoblastoma. The cure rate was 100%, based on the disappearance of pain after a minimum follow-up of 6 months. CONCLUSION: Use of radioguided surgery in the surgical treatment of osteoid osteoma showed satisfactory results, with 100% efficiency in both lesion location and outcome of treatment and without major postoperative complications.

Insulin resistance in patients with familial combined hyperlipidemia and coronary artery disease.

The minimum model modified by the administration of insulin provides an objective and relatively easily measured index of peripheral sensitivity to insulin which was significantly lower (p <0.02) in familial combined hyperlipidemia (FCH) with ischemic heart disease (IHD) than in FCH without IHD and in control subjects (1.2 +/- 0.6, 1.9 +/- 1.0, 2.9 +/- 1.2 x 10(-4) mU/L/ min, respectively). In patients with FCH, insulin resistance explains, at least in part, their metabolic alterations (hypertension, abnormal glucose tolerance, hyperinsulinemia) and elevated IHD.

Effects of calcium dobesilate on the synthesis of endothelium-dependent relaxing factors in rabbit isolated aorta.

1. Some cardiovascular disturbances which occur in diabetics are a consequence of alterations in vascular contractility as well as in endothelium-dependent relaxation. 2. Calcium dobesilate (DOBE) is a drug used in diabetic retinopathy and its mechanism of action is not yet understood. 3. The aim of this study was to investigate the effects of DOBE on synthesis and release of endothelium-dependent relaxing factor (EDRF) and endothelium-dependent hyperpolarizing factor (EDHF) in rabbit isolated aorta. 4. Endothelium-dependent relaxation induced by acetylcholine (ACh) (10(-8)-(10(-5) M) increased in the presence of DOBE 10(-5) M only when vascular endothelium was kept intact. 5. NG-nitro-L-arginine methyl ester (L-NAME; 10(-8)-10(-4) M progressively decreased the enhancing effect of DOBE on endothelium-dependent relaxation whereas it was progressively increased by L-Arg. 6. DOBE 10(-5) M increased in a non-significant manner endothelium-dependent relaxation induced by ACh when the arteries were incubated with both L-NAME 10(-4) M and indomethacin 10(-5) M. 7. DOBE (10(-6) M and 10(-5) M) was able to scavenge superoxide anion radicals generated by the hypoxanthine/xanthine oxidase reaction. 8. These results provide evidence that DOBE is able to affect the vascular disorders associated with diabetes mellitus since it enhances the synthesis of endothelium-dependent relaxing factors.