Shifting Incidence of Solitary Adenomas in the Era of Minimally Invasive Parathyroidectomy. A Multi-Institutional Study

Background

Previously, when a conventional neck exploration (CNE) without preceding diagnostic imaging was the surgical treatment for patients with primary hyperparathyroidism (pHPT) solitary adenomas were observed in 69–88% of patients. The advent of minimally invasive parathyroidectomy (MIP), aiming at a preoperatively identified parathyroid abnormality may be associated with a different incidence of solitary and multiglandular parathyroid disease.

Materials and Methods

In a cohort of 467 patients with sporadic pHPT who preferentially underwent MIP in four hospitals in the same geographical region, the incidence of solitary adenomas, multiple adenomas, and multiglandular hyperplasia (MGD) was evaluated.

Results

A total of 367 patients were scheduled for MIP; 100 patients underwent a planned CNE. The overall surgical success rate of the first operation was 93%, and the cumulative success rate, including a second operative procedure, was 99%. Normocalcemia resulted from removing 1 abnormal PG in 426 patients (91%) and more than one abnormal gland in 35 patients (8%). A parathyroid carcinoma was diagnosed in four of the 426 patients with a single abnormal gland. Four gland hyperplasia was observed in 1 patient. In hospitals where diagnostic workup usually consisted of ultrasound (US) and computed tomography (CT) the incidence of solitary adenomas was 88%, compared with 96% in hospitals where MIBI, US, and CT were used preoperatively (P = 0.007).

Conclusions

A higher frequency of solitary adenomas was observed than historically reported. The extent of the preoperative workup influences the number of observed solitary adenomas.     

Relation between migraine and size of echocardiographic intrapulmonary right-to-left shunt

An increased prevalence of intrapulmonary right-to-left shunt (RLS) has been shown in patients with migraine. The aim of this study was to determine whether the size of intrapulmonary RLS was associated with migraine with aura (MA+) and migraine without aura (MA-) in subjects screened for hereditary hemorrhagic telangiectasia. A total of 462 consecutive subjects were screened for hereditary hemorrhagic telangiectasia and underwent transthoracic contrast echocardiography. A pulmonary shunt was established when contrast appeared in the left atrium after 4 cardiac cycles. Shunt size was assessed semiquantitatively as small (<30 microbubbles), moderate (30 to 100 microbubbles), or large (>100 microbubbles). A headache questionnaire was completed by 420 subjects (91%). Two independent neurologists diagnosed migraine according to the International Headache Society criteria. Of 420 screened subjects (mean age 43.4 ± 15.4 years, 61.4% women), 44 (10.5%) had MA+ and 45 (10.7%) had MA-. MA+ was an independent predictor for an intrapulmonary RLS (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.36 to 6.47, p=0.006) in multivariate analysis. MA- was not correlated with RLS (OR 1.21, 95% CI 0.56 to 2.64, p=0.60). When comparing patients with MA+ to those without migraine in a multivariate analysis, the presence of an intrapulmonary shunt predicted MA+ (OR 2.5, 95% CI 1.2 to 5.2, p=0.01), as did female gender (OR 3.15, 95% CI 1.29 to 7.65, p<0.01). The correlation of MA+ and RLS could be entirely attributed to large intrapulmonary shunts (OR 7.61, 95% CI 3.11 to 18.61, p<0.001), as small (OR 0.6, 95% CI 0.13 to 2.78, p=0.52) and moderate (OR 1.33, 95% CI 0.35 to 5.02, p=0.68) shunts did not appear to be risk factors for MA+. In conclusion, patients with large intrapulmonary RLS have an increased risk for MA+.     

Ambulatory arterial stiffness index: determinants and outcome

OBJECTIVES: We hypothesized that one minus the slope of diastolic on systolic blood pressure in individual 24-h ambulatory blood pressure recordings (ambulatory arterial stiffness index) might reflect arterial stiffness and predict cardiovascular mortality. METHODS: In volunteers and a population recruited in China, we studied concordance between ambulatory arterial stiffness index and established indexes of arterial stiffness. We assessed the predictive value of ambulatory arterial stiffness index in relation to cardiovascular outcome in Irish hypertensive patients. RESULTS: In 166 healthy volunteers, aged 22-83 years, the correlation coefficient between ambulatory arterial stiffness index and pulse wave velocity was 0.51 (P<0.001). In 348 randomly recruited Chinese, the correlations between ambulatory arterial stiffness index and both the central and peripheral systolic augmentation indexes were significantly stronger than those for 24-h ambulatory pulse pressure, particularly in study participants younger than 40 years. Among normotensive participants, the 95th percentile of the ambulatory arterial stiffness index was 0.55 in 234 Chinese and 0.57 in 1617 Europeans enrolled in the International Database on Ambulatory Blood Pressure Monitoring. The upper boundary of the 95% prediction interval of the ambulatory arterial stiffness index in relation to age ranged from 0.53 at 20 years to 0.72 at 80 years. In 11 291 patients enrolled in the Dublin Outcome Study, both ambulatory arterial stiffness index and 24-h ambulatory pulse pressure significantly predicted cardiovascular mortality. Ambulatory arterial stiffness index was a strong predictor of fatal stroke in normotensive participants, whereas pulse pressure better predicted heart attack in hypertensive patients. CONCLUSION: Ambulatory arterial stiffness index is a novel measure of arterial stiffness, which can be readily determined from ambulatory blood pressure recordings and which independently predicts cardiovascular mortality.     

Progression to hypertension in the non-hypertensive participants in the Flemish Study on Environment, Genes and Health Outcomes

OBJECTIVE: To evaluate the consistency between a randomly recruited Western European population and the participants of the Framingham Heart Study, with respect to the rates and determinants of progression to hypertension. METHODS: Among the non-hypertensive individuals enrolled in the Flemish Study on Environment, Genes and Health Outcomes, we assessed progression from optimal (< 120/80 mmHg), normal (120-129/80-84 mmHg) and high-normal (130-139/85-89 mmHg) blood pressure to hypertension (> or = 140/90 mmHg). Our analysis included 781 women and 675 men (age range 10-77 years) who were followed up for a median of 4.6 years (interquartile range 2.4-8.1 years). Our statistical methods included Kaplan-Meier survival function estimates, the log-rank test and multiple Cox regression. RESULTS: In individuals younger than 50 years, 4-year progression rates associated with optimal, normal and high-normal blood pressure were 7.4% [95% confidence interval (CI) 5.5-9.3], 17.9% (95% CI 14.3-21.6) and 24.5% (95% CI 18.7-30.2), respectively. Corresponding 4-year rates of progression for individuals aged 50 years or older were 16.4% (95% CI 11.2-22.5), 26.3% (95% CI 19.8-32.9) and 54.0% (95% CI 45.7-62.3), respectively. In multivariate Cox regression, blood pressure category and body mass index at baseline were strong predictors of hypertension. Before the age of 50 years, male sex and a fast heart rate were also forerunners of hypertension. CONCLUSIONS: The stepwise increase in incidence of hypertension across the three non-hypertensive blood pressure categories in our cohort was similar to that observed in the Framingham Heart Study. The Framingham findings, which have informed several guidelines, can be extrapolated to a Western European population.     

Body temperature and outcome after stroke thrombolysis

AIMS: We studied whether baseline body temperature and temperature increases after stroke adversely affect outcome after thrombolysis with intravenous tissue plasminogen activator (IV tPA). METHODS: The evolution of body temperature in the first 24 h after treatment with IV tPA was described by calculating the area under the curve of the temperature over time plot relative to temperature at admission (AUCBL) and relative to a standard value of 37 degrees C (AUC37). Temperature parameters were related to functional outcome. RESULTS: The median baseline National Institutes of Health Stroke Scale of 100 consecutive patients was 16 (interquartile range 11-21) and 34 patients had a favourable response to tPA. Patients with an unfavourable outcome had a more important temperature elevation than patients who had a favourable outcome after tPA (+1 degrees C vs +0.6 degrees C, P=0.02), despite similar baseline T and had a higher AUCBL (9.79 vs 5.36, P=0.027) and more frequently showed hyperthermia relative to baseline (82% vs 56%, P=0.011). After adjustment for baseline characteristics, the presence of hyperthermia relative to baseline was associated with a reduced odds of good outcome after thrombolysis (OR 0.34, 95% CI 0.10-0.95, P=0.040). CONCLUSION: Hyperthermia relative to baseline temperature in the 24 h after intravenous thrombolysis is associated with an unfavourable outcome.     

The antihyperalgesic effect of levetiracetam in an inflammatory model of pain in rats: mechanism of action

Background and purpose:

The underlying mechanisms of gastric dysfunction during or after an episode of intestinal inflammation are poorly understood. This study investigated the effects of colitis on the contractile effects of motilin, an important endocrine regulator of gastric motility, in the antrum.

Experimental approach:

Myeloperoxidase (MPO) activity, NF-κB activity and motilin receptor density were determined in the antrum of rabbits 5 days after the induction of 2,4,6-trinitrobenzenesulphonic acid colitis. Smooth muscle and neural responses to motilin were studied in antral smooth muscle strips in vitro.

Key results:

Colitis did not affect MPO activity, but increased NF-κB activity in the antrum. Motilin receptor density in the antrum was not affected. Under control conditions, motilin induced a slowly developing tonic smooth muscle contraction. Five days post-inflammation, tonic contractions to motilin were reduced and preceded by a rapid initial contraction. Other kinases were recruited for the phosphorylation of myosin light chain (MLC) (a multi-functional MLC kinase), and for the inhibition of MLC phosphatase (Rho kinase in addition to protein kinase C) to mediate the motilin-induced contractions during inflammation. Colitis potentiated the cholinergic neural on-contractions in the antrum. This was associated with a hyper-reactivity to motilin and an increased muscle response to ACh.

Conclusions and implications:

Colitis altered the course of the motilin-induced smooth muscle contraction in the antrum. This involved changes in the kinases phosphorylating MLC. Increased cholinergic excitability to motilin in the antrum may play a role in the pathogenesis of inflammation-associated gastric motility disorders.     

Heterogeneity and prediction of hemodynamic responses to dobutamine in patients with septic shock

OBJECTIVE: To establish the heterogeneity of hemodynamic responses to dobutamine in patients with septic shock and to identify the predictive factors of these hemodynamic responses. DESIGN: Prospective study. SETTING AND PATIENTS: A total of 12 patients with septic shock in a tertiary medical intensive care unit. INTERVENTIONS: A 20-min dobutamine infusion at 5 microg.kg(-1).min(-1) with subsequent increments to 8, 12.6, and 20 microg.kg(-1).min(-1), on two consecutive days. Responses were dichotomized into changes in heart rate (HR) or stroke volume index (SVI) of >10% and < or =10% at the maximal dobutamine infusion. MEASUREMENTS AND MAIN RESULTS: No differences were found in survival, Acute Physiology and Chronic Health Evaluation II score, maximal dobutamine doses, or pharmacokinetics of dobutamine between HR and SVI groups. In DeltaHR > 10% vs. DeltaHR < or = 10%, baseline HR was lower, and baseline mixed venous oxygen tension and saturation were higher. During dobutamine infusion, mean arterial pressure decreased in DeltaHR > 10%. Cardiac index and the systemic oxygen delivery index increased and the systemic vascular resistance index decreased at unchanged SVI. Pressure work index increased and the ratio of the diastolic to systolic aortic pressure time indices decreased but not to <0.6. In DeltaHR < or = 10%, systemic vascular resistance index and the ratio of the diastolic to systolic aortic pressure time indices decreased (but remained >0.6) without changes in SVI or cardiac index. Baseline hemodynamic and metabolic variables did not differ between SVI groups. In DeltaSVI > 10%, cardiac index increased with dobutamine, but Pao2 and the systemic oxygen delivery index decreased. In DeltaSVI < or = 10%, HR and the systemic oxygen delivery index increased; mean arterial pressure, left ventricular stroke work index, systemic vascular resistance index, and the ratio of the diastolic to systolic aortic pressure time indices decreased. CONCLUSIONS: Patients with a positive chronotropic response to dobutamine had lower baseline HR values, and a chronotropic rather than inotropic response predicted an increase in cardiac index and systemic oxygen delivery index. Incremental dosages of dobutamine did not compromise indirectly measured myocardial oxygen balance.     

Carotid angioplasty and stenting: caveat emptor!

Carotid endarterectomy effectively reduces stroke in patients with TIA or minor stroke and a high-grade carotid stenosis. Carotid endarterectomy is also beneficial in male asymptomatic patients younger than 75 years with high-grade stenosis. Carotid stenting has not been as thoroughly evaluated as carotid endarterectomy in randomized trials. The few trials that have been performed up to now show either inferior results or suggest equivalence. Before accepting carotid stenting as a mainstream treatment for carotid stenosis, this therapy should be as critically evaluated as carotid endarterectomy was in the 1980s and 1990s.     

Meta-analysis of determinants for pet ownership in 12 European birth cohorts on asthma and allergies: a GA2LEN initiative

Background: Studies on pet ownership as a risk or protective factor for asthma and allergy show inconsistent results. This may be on account of insufficient adjustment of confounding factors. Aim: The objective of this study was to describe determinants of cat and dog ownership in European families with and without allergies. Methods: Within the EU‐funded network of excellence GA²LEN, we performed meta‐analyses with data from 12 ongoing European birth cohort studies on asthma and allergy. Each of the birth cohort studies enrolled between 485 and 4089 children. Pet ownership, allergic status (asthma, allergic rhinitis, eczema) of parents and siblings, parental education, access to ground floor, and number of people living at home were assessed by questionnaires. Results: Among the 25 056 families from seven European countries cats (14.9%) were more common than dogs (12.0%). Allergic family history significantly reduced the odds to own a cat (adjusted combined random‐effect OR 0.91; 95% CI 0.85–0.99), or dog (0.90; 0.86–0.94). A higher parental educational level had even more pronounced effects on cat (0.84; 0.71–0.98), and dog ownership (0.61; 0.54–0.70). Elder siblings reduced the odds to own cats, but not dogs. Convenient ground access significantly increased the odds, whereas crowding at home was not associated with cat or dog ownership. Conclusions: The chances to own a cat or dog were significantly reduced in allergic families, in parents with a higher educational level, and in homes without convenient ground access. In addition to parental allergies, social and housing factors should be considered as potential confounders in studies on pet exposure and allergic diseases.