Differences in intraoperative and surgical outcomes between normotensive pheochromocytomas and sympathetic paragangliomas (PPGLs) and hypertensive PPGLs: results from the PHEO-RISK STUDY.

PURPOSE: To compare the intraoperative and surgical outcomes of normotensive pheochromocytomas and sympathetic paragangliomas (PPGLs), hypertensive PPGLs and non-PPGL adrenal lesions. METHODS: This a retrospective multicenter cohort study of patients with PPGLs from 18 tertiary hospitals. A control group of histologically confirmed adrenocortical adenomas (non-PPGL group) was selected to compare intraoperative and surgical outcomes with of the normotensive PPGLs. RESULTS: Two hundred and ninety-six surgeries performed in 289 patients with PPGLs were included. Before surgery, 209 patients were classified as hypertensive PPGLs (70.6%) and 87 as normotensive PPGLs. A higher proportion of normotensive PPGLs than hypertensive PPGLs did not receive alpha presurgical blockade (P = 0.009). When we only considered those patients who received presurgical alpha blockers (200 hypertensive PPGLs and 76 normotensive PPGLs), hypertensive PPGLs had a threefold higher risk of intraoperative hypertensive crisis (OR 3.0 [95% 1.3-7.0]) and of hypotensive episodes (OR 2.9 [95% CI 1.2-6.7]) than normotensive PPGLs. When we compared normotensive PPGLs (n = 76) and non-PPGLs (n = 58), normotensive PPGLs had a fivefold higher risk of intraoperative complications (OR 5.3 [95% CI 1.9-14.9]) and a six times higher risk of postoperative complications (OR 6.1 [95% CI 1.7-21.6]) than non-PPGLs. CONCLUSION: Although the risk of intraoperative hypertensive and hypotensive episodes in normotensive PPGLs is significantly lower than in hypertensive PPGLs, normotensive PPGLs have a greater risk of intraoperative and postoperative complications than non-PPGL adrenal lesions. Therefore, it is recommended to follow the standard of care for presurgical and anesthetic management of PPGLs also in normotensive PPGLs.

Efficacy and safety of ossein-hydroxyapatite complex versus calcium carbonate to prevent bone loss.

Objective: This study aimed to compare the efficacy and safety of ossein-hydroxyapatite complex (OHC) versus calcium carbonate (CC) for preventing bone loss during perimenopause in current clinical practice.Methods: The prospective, comparative, non-randomized, open-label study included 851 perimenopausal women with basal bone mineral density (BMD) T-score ≥-2 standard deviations (SDs). Participants received either OHC (712 mg calcium/day) or CC (1000 mg calcium/day) over 3 years. BMD was evaluated by dual-energy X-ray absorptiometry at the lumbar spine (L2-L4) at baseline and after 18 and 36 months of follow-up. Adverse drug reactions (ADRs) were also recorded.Results: In women receiving OHC, BMD at the L2-L4 site remained stable over the 3-year follow-up period (mean [SD] change 0.00 [0.11] g/cm2). BMD in the CC arm decreased -3.1% (mean [SD] - 0.03 [0.11] g/cm2). Between-group differences were statistically significant (p < 0.001) and favored OHC. ADRs were more frequent in the CC group (7.7% vs. 2.7% in the OHC group; p = 0.001), affecting primarily the gastrointestinal system.Conclusion: OHC showed greater efficacy and tolerability than CC for bone loss prevention in perimenopausal women in real-world practice. As the daily dose of calcium was higher in the CC group, the differences might be linked to the ossein compound in OHC.

Temporal expression of cytokines and signal transducer and activator of transcription factor 3 activation after neonatal hypoxia/ischemia in mice.

Hypoxia/ischemia (HI) is a prevalent reason for neonatal brain injury with inflammation being an inevitable phenomenon following such injury; but there is a scarcity of data regarding the signaling pathway involved and the effector molecules. The signal transducer and activator of transcription factor 3 (STAT3) is known to modulate injury following imbalance between pro- and anti-inflammatory cytokines in peripheral and central nervous system injury making it a potential molecule for study. The current study investigates the temporal expression of interleukin (IL)-6, IL-1ß, tumor necrosis factor-α, IL-1ra, IL-4, IL-10, IL-13 and phosphorylated STAT3 (pSTAT3) after carotid occlusion and hypoxia (8% O2, 55 min) in postnatal day 7 C57BL/6 mice from 3 h to 21 days after hypoxia. Protein array illustrated notable changes in cytokines expressed in both hemispheres in a time-dependent manner. The major pro-inflammatory cytokines showing immediate changes between ipsi- and contralateral hemispheres were IL-6 and IL-1ß. The anti-inflammatory cytokines IL-4 and IL-13 demonstrated a delayed augmentation with no prominent differences between hemispheres, while IL-1ra showed two distinct peaks of expression spread over time. We also illustrate for the first time the spatiotemporal activation of pSTAT3 (Y705 phosphorylation) after a neonatal HI in mice brain. The main regions expressing pSTAT3 were the hippocampus and the corpus callosum. pSTAT3+ cells were mostly a subpopulation of activated astrocytes (GFAP+) and microglia/macrophages (F4/80+) seen only in the ipsilateral hemisphere at most time points studied (till 7 days after hypoxia). The highest expression of pSTAT3+ cells was observed to be around 24-48 h, where the presence of pSTAT3+ astrocytes and pSTAT3+ microglia/macrophages was seen by confocal micrographs. In conclusion, our study highlights a synchronized expression of some pro- and anti-inflammatory cytokines, especially in the long term not previously defined. It also points towards a significant role of STAT3 signaling following micro- and astrogliosis in the pathophysiology of neonatal HI-related brain injury. In the study, a shift from pro-inflammatory to anti-inflammatory cytokine profile was also noted as the injury progressed. We suggest that while designing efficient neuroprotective therapies using inflammatory molecules, the time of intervention and balance between the pro- and anti-inflammatory cytokines must be considered.

Usefulness of antimicrobial susceptibility in the eradication of Helicobacter pylori.

The rate of eradication of Helicobacter pylori with standard triple therapy using omeprazole, amoxicillin and clarithromycin (OAC) is unacceptable in populations with high rates of clarithromycin resistance (15-20%). The aim of this study was to compare the efficacy of 10-day OAC therapy as the first-line treatment in patients diagnosed by culture with antimicrobial susceptibility or diagnosed by a (13) C-labelled urea breath test (UBT) without antimicrobial susceptibility in an area where the clarithromycin resistance rate was 15-20%. This was a retrospective cohort study of 266 patients, recruited consecutively throughout 2008. A total of 247 H. pylori-infected patients received antibiotic therapy (221 received the 10-day OAC therapy and 26 received other regimens) of which 134 patients were diagnosed by culture of gastric samples followed by antimicrobial susceptibility testing and 113 were diagnosed by UBT. In all patients, the eradication of H. pylori was checked by UBT. The cost of eradication by 10-day OAC treatment was assessed in each patient. The success rate of 10-day OAC therapy in patients diagnosed by culture and by UBT was 88% (103/117) and 49% (51/104), respectively (p <0.0005). The treatment was also more cost-effective in the former of these two groups (€571 versus €666). To perform culture and antimicrobial susceptibility of the H. pylori isolates was a more successful and cost effective strategy than empirical 10-day OAC treatment in populations with high rates of resistance to clarithromycin.

Nutrition in systemic sclerosis.

Systemic sclerosis is a connective tissue disease characterized by inflammation and fibrosis of multiple organs (skin, gastrointestinal tract, lung, kidney and heart). After the skin, the organ most affected with a frequency of 75 to 90%, the gastrointestinal tract is more often involved. Gastrointestinal tract involvement is manifested by the appearance of oropharyngeal dysphagia, esophageal dysphagia, gastroesophageal reflux, gastroparesis, pseudo-obstruction, bacterial overgrowth and intestinal malabsorption, constipation, diarrhea and/or fecal incontinence. These effects influence food intake and intestinal absorption leading to the gradual emergence of nutritional deficiencies. About 30% of patients with systemic sclerosis are at risk of malnutrition. In 5-10%, gastrointestinal disorders are the leading cause of death. Therapeutic strategies currently available are limited and aimed at reducing clinical symptoms. The multidisciplinary management of these patients, including nutritional intervention, helps improve gastrointestinal symptoms, and avoid malnutrition, morbidity and improve quality of life.

Asymptomatic bilateral adrenal pheochromocytoma in a patient with a germline V804M mutation in the RET proto-oncogene.

UNLABELLED: A diagnosis of bilateral pheochromocytoma warrants exclusion of hereditary pheochromocytoma. OBJECTIVE: To describe the first case of a bilateral pheochromocytoma associated with V804M mutation in the RET proto-oncogene. PATIENTS: The index case was a 54-year-old man with bilateral adrenal masses discovered during a CT scan performed for other reasons. MEASUREMENTS: Genetic analysis included exons 8-11 and 13-17 in the RET proto-oncogene, all four exons and flanking intronic regions in the SDHD gene, all eight exons and flanking intronic regions in the SDHB, and all three exons in the VHL gene. RESULTS: Investigations revealed elevated urinary metanephrines (32.3 micromol/day), and laparoscopic bilateral adrenalectomy confirmed bilateral pheochromocytomas. A heterozygous V804M mutation in exon 14 of the RET was found in the index case and in four relatives. Total thyroidectomy, performed in four of five affected members in this kindred, disclosed a medullary thyroid carcinoma in the index case and in a 50-year-old woman, and nodular C-cell hyperplasia in the other two subjects. CONCLUSIONS: This clinical case suggests that individuals carrying the germline V804M mutation should be screened annually for the presence of pheochromocytoma.

[Obesity and inflammation]. / Obesidad e inflamación.

The adipose tissue produces a vast number of molecules called adipokines such as leptin, tumoral necrosis factor (TNFalpha), interleukins and adiponectin. Many of the metabolic disturbances associated with obesity and the metabolic syndrome may be due to citokine production by adipocytes. The adipose tissue increases the soluble fractions of TNFalpha leading to a rise in its biological activity. The activation of TNFalpha system causes insulin resistance through different mechanisms such as defects in receptor fosforilation and reduction in insulin-sensitive glucose transporters. TNFalpha is also involved in the pathophysiology of hypertension and dyslipidaemia associated with obesity and insulin resistance. More than one third of interleukin-6 (IL-6) concentrations come from the adipocytes. It has been demonstrated a role for IL-6 in the development of hyperlipidemia, diabetes and hypertension. In contrast to the rest of adipokines, adiponectin is reduced in obesity, diabetes or cardiovascular disease. Adiponectin improves insulin resistance, dyslipidaemia and adhesion to endothelial cells protecting from atherosclerosis development. Thus, adipokines have an important role in the pathophysiology of metabolic syndrome by different mechanisms involving metabolic and vascular effects.

Management of osteoporosis in general practice: a cross-sectional survey of primary care practitioners in Spain.

A cross-sectional survey was conducted to determine the current situation in Spain regarding diagnosis and care of patients with osteoporosis in the primary care setting. A total of 2,500 primary care physicians who were homogeneously grouped in autonomous communities throughout the country received a postal 30-item anonymous self-administered questionnaire. The questionnaire covered demographics and personal characteristics of the physicians, conditions in everyday consultation, and degree of knowledge with regard to risk factors, diagnosis, treatment, and follow-up of the disease. The overall response was 850 (34%). The mean age of physicians surveyed was 43 years (range 23-66 years). The percentage of physicians specialized in community and family medicine was 46.7%. In 55.2% of cases, years of practice ranged between 11 and 20, and 55.7% of physicians visited between 31 and 50 patients per day. Age and years of practice were not associated with daily number of visits. Only 4% of physicians stated that there were specific programs for osteoporosis implemented in their primary care center. Diagnostic complementary investigations that could be ordered included plain radiographs in 96.2% of cases and bone densitometry in 27.8%. Laboratory tests included serum hormones in 61.6% of cases, PTH in 50.2%, and bone alkaline phosphatase in 33.4%. The diagnosis of osteoporosis was made always personally in 25.2% of cases. Personal diagnosis and follow-up, as well as actions directed to detection of osteoporosis were significantly higher among physicians working in centers with specific programs for osteoporosis. With regard to knowledge about osteoporosis, the mean percentage of correct responses was 63%. The percentage of correct responses was inversely associated with age and years of practice, and positively associated with speciality of community and family medicine. Primary care providers are in a good position to assess risk factors and recommend prevention strategies, as well as to play an active role in the diagnosis, care, and follow-up of patients with osteoporosis. Practitioners of younger age and relatively few years of practice were those with more up-to-date information regarding the disease, and the existence of a specific program for osteoporosis seems to improve the management of this condition.

[FMRP immunodetection on hair roots: application to the diagnosis of fragile X syndrome]. / Estudio de la proteína FMRP en la raíz de cabello: aplicación al diagnóstico del síndrome del cromosoma X frágil.

INTRODUCTION: Fragile X syndrome is the most common inherited form of mental retardation. The absence of FMRP protein, codified by the FMR1 gene, results in fragile X phenotype. DNA-based diagnostic methods determine the length of the CGG repeat within the FMR1 gene, the main mutation causing the syndrome. Immunohistochemical diagnostic tests detect all mutations leading to the absence of FMRP expression. Results of the antibody test on hair roots correlate with intellectual quotient in affected men and women. PATIENTS AND METHODS: Immunohistochemical techniques were used to study FMRP expression in hair roots in a control group to establish the correlation with the length of the CGG repeat. Subsequently, 65 girls and boys with mental retardation attending special schools were screened by using the FMRP test on hair roots. RESULTS: Males and females molecularly characterized as within the normal and premutated range expressed FMRP in more than 70 % of hair roots. Full mutation carriers expressed FMRP in less than 70 % of hair roots. Immunohistochemical studies in males and females with mental retardation led to the identification of one affected male. CONCLUSIONS: Fragile X syndrome detection by immunohistochemical testing of hair roots is a valid method of population screening because of the relative noninvasiveness of obtaining samples, and the ease and rapidness of the technique, which can be applied to routine clinical practice.

Macrovascular events after kidney-pancreas transplantation in type 1 diabetic patients.

BACKGROUND: There are few studies concerning the effect of kidney-pancreas transplantation (KPTx) on the progression of macrovascular disease in type 1 diabetic patients. The aim of our study was to retrospectively evaluate the incidence of macrovascular events after functioning KPTx. MATERIALS AND METHODS: We studied 146 patients (96 men and 50 women) who had undergone KPTx from February 1983 to September 2001, with more than 1 year of evolution of both grafts functioning normally. The mean follow-up of the patients after KPTx was 5+/-3 years. RESULTS: Before KPTx, 29 patients displayed 42 macrovascular events. During the follow-up after transplantation, intermittent claudication remained in 25 patients (86.2%) with 11 new macrovascular events (1 stroke, 1 angina pectoris, 1 myocardial infarction, and 8 minor amputations) in 10 patients (34%). Among the 117 patients without antecedent macrovascular events prior to KPTx, 38 (32.5%) experienced a total of 63 macrovascular events (26 intermittent claudication, 4 stroke, 8 angina pectoris, 7 myocardial infarction, 11 minor amputations, and 7 major amputations). Before transplantation, 88.4% of the patients presented with hypertension, 42.5% a history of smoking, and 14.4% previous treatment for dyslipidmia. After transplantation, we observed an important reduction in the percentage of patients with hypertension (48.6%) and smoking (25.5%), without a change in the prevalence of dyslipemia (19.9%). Hypertension after transplantation was clearly associated with the appearance or persistence of macrovascular events. CONCLUSION: In our experience, 43% of the transplant recipients present with macrovascular events. It is important to note the elevated prevalence of cardiovascular risk factors in the patients who underwent KPTx.

Abrupt onset of diabetes during interferon-alpha therapy in patients with chronic hepatitis C.

INTRODUCTION: Interferon-alpha (IFN-alpha) is now widely used in the treatment of chronic hepatitis C. Few patients have been reported as developing impaired glucose tolerance or diabetes mellitus (DM) using this therapy. The explanation for the development of DM in chronic hepatitis C treated with IFN-alpha is unclear. We report two patients who developed an abrupt onset of diabetes during IFN-alpha for chronic hepatitis C. CASE REPORTS: Two male middle-aged patients were admitted to our hospital for an abrupt onset of diabetes, in diabetic ketoacidosis, with a very short duration of hyperglycaemic symptoms. Their clinical course was similar. Case 1 never demonstrated any markers of pancreatic immunogenicity. Case 2 had high levels of decarboxylase glutamic acid autoantibodies (GADAb), before the IFN-alpha treatment that persisted. We compared initial beta-cell function and metabolic control with a group of middle-aged patients from our hospital who had recently been diagnosed with Type 1 diabetes mellitus (DM1). In contrast to these, the onset of the disease was particularly severe with beta-cell function substantially impaired and displaying unstable short-term metabolic control. CONCLUSIONS: Type 1 diabetes should be considered as a potential complication if IFN is administered to patients with chronic hepatitis C. Its onset may be severe and result in short-term difficulties in metabolic control.