Fatal intracranial haemorrhage occurring after oral anticoagulant treatment initiation for secondary stroke prevention in patients with atrial fibrillation.

BACKGROUND AND PURPOSE: In this pooled analysis of seven multicentre cohorts potential differences were investigated in the incidence, characteristics and outcomes between intracranial haemorrhages (ICHs) associated with the use of non-vitamin K antagonist oral anticoagulants (NOAC-ICH) or with vitamin K antagonists (VKA-ICH) in ischaemic stroke patients after oral anticoagulant treatment initiation for atrial fibrillation (AF). METHODS: Data from 4912 eligible AF patients who were admitted in a stroke unit with ischaemic stroke or transient ischaemic attack and who were treated with either VKAs or NOACs within 3 months post-stroke were included. Fatal ICH was defined as death occurring during the first 30 days after ICH onset. A meta-analysis of available observational studies reporting 30-day mortality rates from NOAC-ICH or VKA-ICH onset was additionally performed. RESULTS: During 5970 patient-years of follow-up 71 participants had an ICH, of whom 20 were NOAC-ICH and 51 VKA-ICH. Patients in the two groups had comparable baseline characteristics, except for the higher prevalence of kidney disease in VKA-ICH patients. There was a non-significant higher number of fatal ICH in patients with VKAs (11 events per 3385 patient-years) than in those with NOACs (three events per 2623 patient-years; hazard ratio 0.32, 95% confidence interval 0.09-1.14). Three-month functional outcomes were similar (P > 0.2) in the two groups. The meta-analysis showed a lower 30-day mortality risk for patients with NOAC-ICH compared to VKA-ICH (relative risk 0.70, 95% confidence interval 0.51-0.95). CONCLUSIONS: Non-vitamin K oral anticoagulants for intracranial haemorrhages and VKA-ICH occurring during secondary stroke prevention of AF patients have comparable baseline characteristics and outcomes except for the risk of fatal ICH within 30 days, which might be greater in VKA-ICH.

Fast-track versus long-term hospitalizations for patients with non-disabling acute ischaemic stroke.

BACKGROUND AND PURPOSE: The aim was to assess the feasibility and safety of fast-track hospitalizations in a selected cohort of patients with stroke. METHODS: Patients hospitalized at the Stroke Center of the University Hospital Basel, Switzerland, with an acute ischaemic stroke confirmed on magnetic resonance diffusion-weighted imaging were included. Neurological deficits of the included patients were non-disabling, i.e. not interfering with activities of daily living and compatible with a direct discharge home. Patients with premorbid disability were excluded. All patients were admitted to the Stroke Center for ≥24 h. Two study groups were compared - fast-track hospitalizations (≤72 h) and long-term hospitalizations (>72 h). The primary end-point was a composite of any unplanned rehospitalization for any reason within 3 months since hospital discharge and a modified Rankin Scale 3-6 at 3 months. Adjustment for confounders was done using the inverse probability of treatment weights (IPTW). RESULTS: Amongst the 521 patients who met the inclusion criteria, fast-track hospitalizations were performed in 79 patients (15%). In the fast-track group, seven patients (8.9%) met the primary end-point, compared to 37 (8.4%) in the long-term group [odds ratio (OR) 1.06, 95% confidence interval (CI) 0.42-2.34, P = 0.88]. After weighting for IPTW, the odds of the primary end-point remained similar between the two arms (ORIPTW 1.27, 95% CI 0.51-3.16, P = 0.61). The costs of fast-track hospitalizations were lower, on average, by $4994. CONCLUSIONS: Fast-track hospitalizations including a full workup proved to be feasible, showed no increased risk and were less expensive than long-term hospitalizations.

Management of patients with stroke treated with direct oral anticoagulants.

Since their market approval, direct oral anticoagulants (DOACs) are being increasingly used for stroke prevention in patients with atrial fibrillation. However, the management of DOAC-treated patients with stroke poses several challenges for physicians in everyday clinical practice, both in the acute setting and in long-term care. This has spurred extensive research activity in the field over the past few years, which we review here.

Impact of body mass index on outcome in stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: The impact of body mass index (BMI) on outcome in stroke patients treated with intravenous thrombolysis (IVT) was investigated. METHODS: In a multicentre IVT-register-based observational study, BMI with (i) poor 3-month outcome (i.e. modified Rankin Scale scores 3-6), (ii) death and (iii) symptomatic intracranial haemorrhage (sICH) based on criteria of the ECASS II trial was compared. BMI was used as a continuous and categorical variable distinguishing normal weight (reference group 18.5-24.9 kg/m2 ) from underweight (<18.5 kg/m2 ), overweight (25-29.9 kg/m2 ) and obese (≥30 kg/m2 ) patients. Univariable and multivariable regression analyses with adjustments for age and stroke severity were done and odds ratios with 95% confidence intervals [OR (95% CI)] were calculated. RESULTS: Of 1798 patients, 730 (40.6%) were normal weight, 55 (3.1%) were underweight, 717 (39.9%) overweight and 295 (16.4%) obese. Poor outcome occurred in 38.1% of normal weight patients and did not differ significantly from underweight (45.5%), overweight (36.1%) and obese (32.5%) patients. The same was true for death (9.5% vs. 14.5%, 9.6% and 7.5%) and sICH (3.9% vs. 5.5%, 4.3%, 2.7%). Neither in univariable nor in multivariable analyses did the risks of poor outcome, death or sICH differ significantly between BMI groups. BMI as a continuous variable was not associated with poor outcome, death or sICH in unadjusted [OR (95% CI) 0.99 (0.97-1.01), 0.98 (0.95-1.02), 0.98 (0.94-1.04)] or adjusted analyses [OR (95% CI) 1.01 (0.98-1.03), 0.99 (0.95-1.05), 1.01 (0.97-1.05)], respectively. CONCLUSION: In this largest study to date, investigating the impact of BMI in IVT-treated stroke patients, BMI had no prognostic meaning with regard to 3-month functional outcome, death or occurrence of sICH.

Obesity in the ageing man.

As the population is ageing globally, both ageing and obesity are recognized as major public health challenges. The aim of this narrative review is to present and discuss the current evidence on the changes in body composition, energy balance and endocrine environment that occur in the ageing man. Obesity in the ageing man is related to changes in both body weight and composition due to alterations in energy intake and total energy expenditure. In addition, somatopenia (decreased GH secretion), late-onset hypogonadism (LOH), changes in thyroid and adrenal function, as well as changes in appetite-related peptides (leptin, ghrelin) and, most importantly, insulin action are related to obesity, abnormal energy balance, redistribution of the adipose tissue and sarcopenia (decreased muscle mass). A better understanding of the complex relationship of ageing-related endocrine changes and obesity could lead to more effective interventions for elderly men.

Secondary osteoporosis - an endocrinological approach focusing on underlying mechanisms.

Osteoporosis is a major and increasingly serious public health problem not only in postmenopausal women and people over 70 years old (primary osteoporosis) but also in men under 70 years and premenopausal women (secondary osteoporosis). The most common primary osteoporosis occurs as a result of menopause and aging process. Secondary osteoporosis is a consequence of an underlying cause and frequently is diagnosed after an atraumatic fracture. The pathogenesis of secondary osteoporosis is almost always multifactorial. Certain endocrinopathies, systemic diseases, malignant neoplasias, organ dysfunctions, a variety of medications such as corticosteroids, lifestyle conditions and habits, and also major depression can lead to the secondary osteoporosis. Early diagnosis and treatment can prevent further bone loss and fractures.

Seronegative myasthenia gravis and Graves' disease. Is there a link?

Graves' disease (GD) and myasthenia gravis (MG) are common autoimmune diseases but their coexistence is very rare. They may possibly share the same pathogenetic mechanisms. Recent research has shown the involvement of autoantibodies, lymphocytes, cytokines and chemokines in the pathogenesis of MG and GD. It appears that Th17 cell lineage is involved in autoimmune thyroid disease (AITD) and seems to be key factor in the development of both MG and GD.A 34-year-old male with seronegative myasthenia gravis due to thymic hyperplasia was diagnosed with also GD and opthalmopathy. Several diagnostic and therapeutic issues regarding the relevant literature are discussed.

Environmental endocrine disruptors and obesity.

UNLABELLED: Obesity has recently become an epidemic. The rise in the childhood obesity incidence is of particular concern. High density caloric diets and physical inactivity are the main causes of obesity. Besides that, is generally accepted that obesity has a genetic predisposition, unchanged for the past few decades. The environment via endocrine disruptors might be, at least partly responsible for the globally obesity epidemic. Endocrine disruptors are environmental chemical compounds produced by human activity that either mimic or block hormonal actions. Many of them modulate lipid metabolism and adipogenesis, contributing to obesity initiation and/or exacerbation. Here we provide an overview of the role of the environmental chemical obesogens and their impact on obesity. KEYWORDS: obesity, endocrine disruptors, epigenetics.

Medullary thyroid carcinoma surgical cytoreduction induces an increase in serum calcitonin and carcinoembryonic antigen doubling times.

Serum calcitonin (Ct) and carcinoembryonic antigen (CEA) doubling times (DT) are considered to be strong prognostic markers in patients with medullary thyroid carcinoma (MTC). The Objective of this work is to study the effect of MTC debulking on Ct and CEA DTs. 4 patients with MTC are presented who after an initial neck operation had residual disease were followed-up with serial measurements of serum Ct and CEA for several years before and after a secondary incomplete removal of involved cervical lymph nodes. The patients received no other treatment for MTC. Ct and CEA DTs were determined after fitting the Ct or CEA values to an exponential growth equation. In patient A, Ct DT increased from 1.45 years (1.17-1.89, 95% CI) preoperatively, to 5.72 (3.22-25.77) postoperatively. In patient B, Ct DT was 1.63 years (1.36-2.02) preoperatively, and very long (serum Ct practically ceased increasing) postoperatively. In patient C, Ct DT was 4.03 years (2.22-21.58) before, and very long after the operation. In patient D, Ct DT from 1.16 years (0.82-1.99) before, increased to 4.21 years (3.04-6.86) after the operation. The changes in CEA DTs were similar to those of Ct DTs in 2 patients in whom the tumor was apparently producing the protein. In conclusion, surgical MTC cytoreduction in 4 patients caused an increase in the Ct and CEA DTs, and the patients could be reclassified in new Ct DT-based strata with better prognosis than before the operation. We hypothesize that such tumor burden reduction may slow the growth of any residual MTC and we discuss mechanisms that could be responsible for this phenomenon.

Bone mineral density and bone metabolism in hemodialysis patients. Correlation with PTH, 25OHD3 and leptin

Background: Bone metabolism disorders in hemodialysed patients (HD) involve several humoral factors, of which PTH plays the central role. Leptin is usually found increased in renal failure and its link with bone metabolism has not been elucidated. We investigated the BMD and bone metabolism in association with serum PTH, 25OHD3 and leptin in HD patients. Methods: We measured bone alkaline phosphatase (bSAP), cross linked N telopeptide of type 1 collagen (NTx), PTH, 25OHD3 and leptin in 37 HD patients. We also evaluated BMI and BMD in lumbar spine (LS) and in femoral neck (FN) by DXA. Statistical evaluations were based on simple regression analysis. Results: 1) Osteopenia was found in 32,1% in LS and 50% in FN and osteoporosis in 14.3% and 21.4% of our patients, respectively. LS or FN Z score was not related to HD duration. 2) Bone markers, PTH, phosphorus and leptin levels were increased. 3) 25OHD3 was low and was not related to NTx, bSAP or PTH. 4) PTH correlated with bone markers and Z score in LS and FN. 5) Leptin had no correlation with bone markers or Z score (except BMI). Conclusions: In our hemodialysed patients bone metabolism markers were increased in relation with high serum PTH levels. The observed high serum leptin was not associated with bone metabolism. Additionally the duration of hemodialysis did not appear to affect bone density (AU)

Antecedentes: Los trastornos del metabolismo óseo en pacientes en hemodiálisis (HD) implican varios factores humorales, de los cuales la función central recae sobre la hormona paratiroidea. Cuando hay insuficiencia renal normalmente se detectan niveles elevados de leptina y su relación con el metabolismo óseo está aún por esclarecer. Investigamos la densidad mineral ósea (DMO) y el metabolismo óseo en relación con la hormona paratiroidea sérica, el 25(OH)D3 y la leptina en pacientes en HD. Métodos: Medimos la fosfatasa alcalina ósea (FAO), el telopéptido N, la hormona paratiroidea, el 25(OH)D3 y la leptina en 37 pacientes en HD. Asimismo, evaluamos el IMC y la DMO en la columna lumbar (CL) y en el cuello femoral (CF) mediante DXA. Las evaluaciones estadísticas se basaron en análisis de regresión simples. Entrecruzamiento del telopéptido N del colágeno óseo tipo I. Resultados: 1) De nuestros pacientes, el 32,1% presentaba osteopenia en CL y 50% en CF y el 14,3% y el 21,4% osteoporosis, respectivamente. El puntaje Z en CL o CF no estaba relacionado con la duración de la HD. 2) Los marcadores óseos, la hormona paratiroidea, y los niveles de fósforo y leptina se vieron incrementados. 3) El 25(OH)D3 era bajo y no estaba relacionado con el telopéptido N, la FAO o la hormona paratiroidea. 4) La hormona paratiroidea estaba correlacionada con los marcadores óseos y con el puntaje Z en CL y CF. 5) La leptina no presentaba correlación con los marcadores óseos o con el puntaje Z (con excepción del IMC). Conclusiones: En nuestros pacientes en hemodiálisis, los marcadores del metabolismo óseo se vieron incrementados en relación con los niveles elevados de hormona paratiroidea sérica. La elevada leptina sérica observada no estaba asociada al metabolismo óseo. Además, la duración de la hemodiálisis no pareció afectar a la densidad ósea (AU)

Primary umbilical endometriosis: case report and literature review.

We present a case of primary endometriosis of the umbilicus in a young nulliparous patient without any previous history of abdominal or pelvic surgery. Primary endometriosis of extra pelvic sites is unusual while umbilical endometriosis is quite rare. Diagnosis of endometriosis is difficult to obtain and sometimes diagnoses can be false-positive or false-negative. Some imaging procedures can be done to rule out other disorders but it is difficult to differentiate them from endometriosis. A definite diagnosis can only be established by histopathological examination. Hematoxylin and eosin (H&E) is the staining of choice. Conservative surgical excision of the lesion and drugs such as oral contraceptives and gonadotropin releasing analogues are the first-line treatment.

Bone mineral density and bone metabolism in hemodialysis patients. Correlation with PTH, 25OHD3 and leptin.

BACKGROUND: Bone metabolism disorders in hemodialysed patients (HD) involve several humoral factors, of which PTH plays the central role. Leptin is usually found increased in renal failure and its link with bone metabolism has not been elucidated. We investigated the BMD and bone metabolism in association with serum PTH, 25OHD3 and leptin in HD patients. METHODS: We measured bone alkaline phosphatase (bSAP), cross linked N telopeptide of type 1 collagen (NTx), PTH, 25OHD3 and leptin in 37 HD patients. We also evaluated BMI and BMD in lumbar spine (LS) and in femoral neck (FN) by DXA. Statistical evaluations were based on simple regression analysis. RESULTS: 1) Osteopenia was found in 32,1% in LS and 50% in FN and osteoporosis in 14.3% and 21.4% of our patients, respectively. LS or FN Z score was not related to HD duration. 2) Bone markers, PTH, phosphorus and leptin levels were increased. 3) 25OHD3 was low and was not related to NTx, bSAP or PTH. 4) PTH correlated with bone markers and Z score in LS and FN. 5) Leptin had no correlation with bone markers or Z score (except BMI). CONCLUSIONS: In our hemodialysed patients bone metabolism markers were increased in relation with high serum PTH levels. The observed high serum leptin was not associated with bone metabolism. Additionally the duration of hemodialysis did not appear to affect bone density.

Effect of an oral glucose load on PTH, 250HD3, calcium, and phosphorus homeostasis in postmenopausal women.

INTRODUCTION. Previous studies particularly in children and neonates have shown that serum calcium declines and parathyroid hormone (PTH) rises during an oral glucose load. However, there is not a general agreement in this regard. This study was carried out to evaluate the effects of an oral glucose load on calcium and phosphorus homeostasis in postmenopausal women along with serum insulin, PTH, and 250HD3 changes. PATIENTS AND METHODS. After an overnight fasting, an oral glucose tolerance test was performed in 50 postmenopausal women; and glucose, insulin, PTH, and D3 were measured at baseline and every 30 min during the 2 hours of the test. RESULTS. Serum glucose and insulin increased as expected and reached their peak values at 60 and 90 min, respectively. PTH and phosphorus decreased significantly and the maximum decline was observed at 30 and 120 min after glucose load (p < 0.0001), respectively. Serum calcium, magnesium, and D3 levels showed no significant changes at any time measured. Serum PTH values had a significant negative correlation with glucose and insulin values (p = 0.026 and p = 0.031, respectively). Serum D3 also correlated negatively with glucose (p = 0.002). CONCLUSION. Our study shows that an oral glucose load induced hyperglycemia/hyperinsulinemia promotes a significant decline in serum PTH and phosphorus levels without changes in calcium or 250HD3 in postmenopausal women.

Heterophilic antibodies causing falsely high serum calcitonin values.

Heterophilic antibodies (HA) may interfere in some immunoassays, causing falsely high hormone values, of which practitioners should be aware when measuring calcitonin (CT) used as tumor marker for medullary thyroid carcinoma (MTC). We studied four patients with thyroid nodules, three of whom underwent surgical neck exploration, after an erroneous diagnosis of MTC because of falsely high serum CT eventually proved to be due to HA. One patient had a lingual thyroid, two autoimmune thyroiditis and the fourth a colloid goiter. The minimal incremental CT response to calcium infusion raised our suspicion of possible false high CT values due to HA. There was no linearity of the CT values obtained by testing serial dilutions of the sera in the CT assay, which employs two monoclonal mouse anti-CT antibodies. Addition of normal mouse gamma globulin eliminated the interference by HA in the sera of two patients. Serum assayed in a polyclonal radioimmunoassay using goat anti-CT antibodies gave normal CT values. Finally, incubation of the sera in Heterophilic Blocking Tubes (HBT) eliminated the false CT immunoreactivity. A spontaneous change of the CT serum concentrations was noticed in three patients over several months, apparently due to changing titles of HA. We suggest that, in patients a) whose CT response to calcium or pentagastrin infusion is minimal despite high basal CT values, b) with autoimmune thyroiditis and c) in whom an unexpected change in serum CT concentrations occurs, the possibility of spuriously high CT values because of circulating HA should be considered.