Postmortem findings in bone cement implantation syndrome-related deaths.

Several mechanisms have been postulated as potentially involved in life-threatening complications during cemented surgery. In this study, we evaluated the role of anaphylaxis and pulmonary fat embolism in the pathophysiology of bone cement implantation syndrome in a series of fatal cases that underwent medicolegal investigations. Postmortem findings in these cases were compared with those obtained from individuals who died after other injuries and/or interventions and in which activated mast cells and pulmonary fat embolism were involved in the pathogenesis of death. Fifty subjects were selected including 6 individuals who had undergone cemented total hip arthroplasty and died intraoperatively, 32 subjects who died shortly after being involved in traffic accidents, 8 individuals who died shortly after the injection of contrast material, and 4 subjects who had undergone orthopedic surgery and died postoperatively. Massive pulmonary fat embolism was determined to be the cause of death in all the 6 subjects who died intraoperatively as well as the main cause of death in traffic-road victims with rapid respiratory function deterioration. Mast cell activation was identified exclusively in the group of subjects who died shortly after contrast material administration. Massive pulmonary fat embolism appears to be the most important factor responsible for severe cardiorespiratory function deterioration during cemented arthroplasty. Cardiac comorbidities can also significantly influence the severity of intraoperative complications, thus corroborating the hypothesis of a multifactorial model in the pathogenesis of bone cement implantation syndrome.

The European Respiratory Society spirometry tent: a unique form of screening for airway obstruction.

In order to raise public awareness of the importance of early detection of airway obstruction and to enable many people who had not been tested previously to have their lung function measured, the European Lung Foundation and the European Respiratory Society (ERS) organised a spirometry testing tent during the annual ERS Congresses in 2004-2009. Spirometry was performed during the ERS Congresses in volunteers; all participants answered a simple, brief questionnaire on their descriptive characteristics, smoking and asthma. Portable spirometers were freely provided by the manufacturer. Nurses and doctors from pulmonary departments of local hospitals/universities gave their service for free. Lower limit of normal (LLN) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for diagnosing and grading airway obstruction were used. Of 12,448 participants in six congress cities, 10,395 (83.5%) performed acceptable spirometry (mean age 51.0 ± 18.4 yrs; 25.5% smokers; 5.5% asthmatic). Airway obstruction was present in 12.4% of investigated subjects according to LLN criteria and 20.3% according to GOLD criteria. Through multinomial logistic regression analysis, age, smoking habits and asthma were significant risk factors for airway obstruction. Relative risk ratio and 95% confidence interval for LLN stage I, for example, was 2.9 (2.0-4.1) for the youngest age (≤ 19 yrs), 1.9 (1.2-3.0) for the oldest age (≥ 80 yrs), 2.4 (2.0-2.9) for current smokers and 2.8 (2.2-3.6) for reported asthma diagnosis. In addition to being a useful advocacy tool, the spirometry tent represents an unusual occasion for early detection of airway obstruction in large numbers of city residents with an important public health perspective.

Papilledema and obstructive sleep apnea syndrome.

OBJECTIVES: To characterize the pathogenesis and clinical features of optic disc edema associated with obstructive sleep apnea syndrome (SAS). METHODS: A series of 4 patients with SAS and papilledema (PE) underwent complete neuro-ophthalmologic evaluation and lumbar puncture. In 1 patient, continuous 24-hour intracranial pressure (ICP) monitoring was also performed. RESULTS: All 4 patients had bilateral PE that was asymmetric in 2. Three patients had optic nerve dysfunction, asymmetric in 1, unilateral in 2. Daytime cerebrospinal fluid pressure measurements were within normal range. Nocturnal monitoring performed in one patient, however, demonstrated repeated episodes of marked ICP elevation associated with apnea and arterial oxygen desaturation. CONCLUSIONS: We propose that PE in SAS is due to episodic nocturnal hypoxemia and hypercarbia resulting in increased ICP secondary to cerebral vasodilation. In these individuals, intermittent ICP elevation is sufficient to cause persistent disc edema. These patients may be at increased risk for developing visual loss secondary to PE compared with patients with obesity-related pseudotumor cerebri because of associated hypoxemia. The diagnosis of SAS PE may not be appreciated because daytime cerebrospinal fluid pressure measurements are normal and because patients tend to present with visual loss rather than with symptoms of increased ICP.

Leukemic cluster growth in culture is an independent risk factor for acute myeloid leukemia and short survival in patients with myelodysplastic syndrome.

In patients with myelodysplastic syndrome (MDS) precursor cell cultures (colony-forming unit cells, CFU-C) can provide an insight into the growth potential of malignant myeloid cells. In a retrospective single-center study of 73 untreated MDS patients we assessed whether CFU-C growth patterns were of prognostic value in addition to established criteria. Abnormalities were classified as qualitative (i.e. leukemic cluster growth) or quantitative (i.e. strongly reduced/absent growth). Thirty-nine patients (53%) showed leukemic growth, 26 patients (36%) had strongly reduced/absent colony growth, and 12 patients showed both. In a univariate analysis the presence of leukemic growth was associated with strongly reduced survival (at 10 years 4 vs. 34%, p = 0.004), and a high incidence of transformation to AML (76 vs. 32%, p = 0.01). Multivariate analysis identified leukemic growth as a strong and independent predictor of early death (relative risk 2.12, p = 0.03) and transformation to AML (relative risk 2.63, p = 0.04). Quantitative abnormalities had no significant impact on the disease course. CFU-C assays have a significant predictive value in addition to established prognostic factors in MDS. Leukemic growth identifies a subpopulation of MDS patients with poor prognosis.

Homozygosity for a novel truncating mutation confirms TBX15 deficiency as the cause of Cousin syndrome.

Cousin syndrome, also called pelviscapular dysplasia (OMIM 260660), is characterized by short stature, craniofacial dysmorphism, and multiple skeletal anomalies. Following its description in two sibs in 1982, no new cases have been observed until the observation of two unrelated cases in 2008 who were homozygous for frameshift mutations in TBX15. We investigated an adult individual with short stature, a complex craniofacial dysmorphism, malformed and rotated ears, short neck, elbow contractures, hypoacusis, and hypoplasia of scapula and pelvis on radiographs. We identified homozygosity for a novel nonsense mutation (c.841C>T) in TBX15 predicted to cause a premature stop (p.Arg281*) with truncation of the protein. This observation confirms that Cousin syndrome is a consistent and clinically recognizable phenotype caused by loss of function of TBX15.

Neonatal and adult ICU ventilators to provide ventilation in neonates, infants, and children: a bench model study.

BACKGROUND: Using a bench test model, we investigated the hypothesis that neonatal and/or adult ventilators equipped with neonatal/pediatric modes currently do not reliably administer pressure support (PS) in neonatal or pediatric patient groups in either the absence or presence of air leaks. METHODS: PS was evaluated in 4 neonatal and 6 adult ventilators using a bench model to evaluate triggering, pressurization, and cycling in both the absence and presence of leaks. Delivered tidal volumes were also assessed. Three patients were simulated: a preterm infant (resistance 100 cm H2O/L/s, compliance 2 mL/cm H2O, inspiratory time of the patient [TI] 400 ms, inspiratory effort 1 and 2 cm H2O), a full-term infant (resistance 50 cm H2O/L/s, compliance 5 mL/cm H2O, TI 500 ms, inspiratory effort 2 and 4 cm H2O), and a child (resistance 30 cm H2O/L/s, compliance 10 mL/cm H2O, TI 600 ms, inspiratory effort 5 and 10 cm H2O). Two PS levels were tested (10 and 15 cm H2O) with and without leaks and with and without the leak compensation algorithm activated. RESULTS: Without leaks, only 2 neonatal ventilators and one adult ventilator had trigger delays under a given predefined acceptable limit (1/8 TI). Pressurization showed high variability between ventilators. Most ventilators showed TI in excess high enough to seriously impair patient-ventilator synchronization (> 50% of the TI of the subject). In some ventilators, leaks led to autotriggering and impairment of ventilation performance, but the influence of leaks was generally lower in neonatal ventilators. When a noninvasive ventilation algorithm was available, this was partially corrected. In general, tidal volume was calculated too low by the ventilators in the presence of leaks; the noninvasive ventilation algorithm was able to correct this difference in only 2 adult ventilators. CONCLUSIONS: No ventilator performed equally well under all tested conditions for all explored parameters. However, neonatal ventilators tended to perform better in the presence of leaks. These findings emphasize the need to improve algorithms for assisted ventilation modes to better deal with situations of high airway resistance, low pulmonary compliance, and the presence of leaks.

Respiratory self-navigated postcontrast whole-heart coronary MR angiography: initial experience in patients.

PURPOSE: To assess the diagnostic performance of respiratory self-navigation for whole-heart coronary magnetic resonance (MR) angiography in a patient cohort referred for diagnostic cardiac MR imaging. MATERIALS AND METHODS: Written informed consent was obtained from all participants for this institutional review board-approved study. Self-navigated coronary MR angiography was performed after administration of a contrast agent in 78 patients (mean age, 48.5 years ± 20.7 [standard deviation]; 53 male patients) referred for cardiac MR imaging because of coronary artery disease (n = 40), cardiomyopathy (n = 14), congenital anomaly (n = 17), or "other" (n = 7). Examination duration was recorded, and the image quality for each coronary segment was assessed with consensus reading. Vessel sharpness, length, and diameter were measured. Quantitative values in proximal, middle, and distal segments were compared by using analysis of variance and t tests. A double-blinded comparison with the results of x-ray angiography was performed when such results were available. RESULTS: When patients with different indications for cardiac MR imaging were examined with self-navigated postcontrast coronary MR angiography, whole-heart data sets with 1.15-mm isotropic spatial resolution were acquired in an average of 7.38 minutes ± 1.85. The main and proximal coronary segments could be visualized in 92.3% of cases, while the middle and distal segments could be visualized in 84.0% and 55.8% of cases, respectively. Subjective scores and vessel sharpness were significantly higher in the proximal segments than in the middle and distal segments (P < .05). Anomalies of the coronary arteries could be confirmed or excluded in all cases. Per-vessel sensitivity and specificity for stenosis detection were 64.7% and 85.0%, respectively, in the 31 patients for whom reference standard x-ray coronary angiography results were available. CONCLUSION: The self-navigated coronary MR angiography sequence shows promise for coronary imaging. However, technical improvements are needed to improve image quality, especially in the more distal coronary segments.

Turner syndrome: evaluation of prenatal diagnosis in 19 European registries.

This study evaluated the prenatal diagnosis of Turner syndrome by ultrasound examination in an unselected population from all over Europe. Data from 19 congenital malformation registries from 11 European countries were analyzed. Turner syndrome was diagnosed in 125 cases (7.2%) in a total of 1,738 chromosome abnormalities. Sixty-seven percent of cases were detected prenatally by ultrasound examination due to the presence of congenital defects. The most frequent anomalies were cystic hygroma (59.5%) and hydrops fetalis (19%). The most frequent karyotype was 45,X (81.6%) followed by different types of mosaicism (16.8%). Significant differences in congenital defects (P = 0.0003) were observed between 45,X karyotypes and 45,X mosaicism cases. Prenatal counseling for 45,X mosaicism should take into account the expectation of a milder phenotype. In 78.6% of cases diagnosed by ultrasound examination due to congenital anomalies, the pregnancy was terminated. Prenatal detection of Turner syndrome by ultrasound examination was high in this unselected population.

Acute respiratory and cardiovascular admissions after a public smoking ban in geneva, Switzerland.

BACKGROUND: Many countries have introduced legislations for public smoking bans to reduce the harmful effects of exposure to tobacco smoke. Smoking bans cause significant reductions in admissions for acute coronary syndromes but their impact on respiratory diseases is unclear. In Geneva, Switzerland, two popular votes led to a stepwise implementation of a state smoking ban in public places, with a temporary suspension. This study evaluated the effect of this smoking ban on hospitalisations for acute respiratory and cardiovascular diseases. METHODS: This before and after intervention study was conducted at the University Hospitals of Geneva, Switzerland, across 4 periods with different smoking legislations. It included 5,345 patients with a first hospitalisation for acute coronary syndrome, ischemic stroke, acute exacerbation of chronic obstructive pulmonary disease, pneumonia and acute asthma. The main outcomes were the incidence rate ratios (IRR) of admissions for each diagnosis after the final ban compared to the pre-ban period and adjusted for age, gender, season, influenza epidemic and secular trend. RESULTS: Hospitalisations for acute exacerbation of chronic obstructive pulmonary disease significantly decreased over the 4 periods and were lowest after the final ban (IRR = 0.54 [95%CI: 0.42-0.68]). We observed a trend in reduced admissions for acute coronary syndromes (IRR = 0.90 [95%CI: 0.80-1.00]). Admissions for ischemic stroke, asthma and pneumonia did not significantly change. CONCLUSIONS: A legislative smoking ban was followed by a strong decrease in hospitalisations for acute exacerbation of chronic obstructive pulmonary disease and a trend for reduced admissions for acute coronary syndrome. Smoking bans are likely to be very beneficial for patients with chronic obstructive pulmonary disease.

Recurrent de novo mitochondrial DNA mutations in respiratory chain deficiency.

Starting from a cohort of 50 NADH-oxidoreductase (complex I) deficient patients, we carried out the systematic sequence analysis of all mitochondrially encoded complex I subunits (ND1 to ND6 and ND4L) in affected tissues. This approach yielded the unexpectedly high rate of 20% mutation identification in our series. Recurrent heteroplasmic mutations included two hitherto unreported (T10158C and T14487C) and three previously reported mutations (T10191C, T12706C and A13514G) in children with Leigh or Leigh-like encephalopathy. The recurrent mutations consistently involved T-->C transitions (p<10(-4)). This study supports the view that an efficient molecular screening should be based on an accurate identification of respiratory chain enzyme deficiency.

Multispectral brain morphometry in Tourette syndrome persisting into adulthood.

Tourette syndrome is a childhood-onset neuropsychiatric disorder with a high prevalence of attention deficit hyperactivity and obsessive-compulsive disorder co-morbidities. Structural changes have been found in frontal cortex and striatum in children and adolescents. A limited number of morphometric studies in Tourette syndrome persisting into adulthood suggest ongoing structural alterations affecting frontostriatal circuits. Using cortical thickness estimation and voxel-based analysis of T1- and diffusion-weighted structural magnetic resonance images, we examined 40 adults with Tourette syndrome in comparison with 40 age- and gender-matched healthy controls. Patients with Tourette syndrome showed relative grey matter volume reduction in orbitofrontal, anterior cingulate and ventrolateral prefrontal cortices bilaterally. Cortical thinning extended into the limbic mesial temporal lobe. The grey matter changes were modulated additionally by the presence of co-morbidities and symptom severity. Prefrontal cortical thickness reduction correlated negatively with tic severity, while volume increase in primary somatosensory cortex depended on the intensity of premonitory sensations. Orbitofrontal cortex volume changes were further associated with abnormal water diffusivity within grey matter. White matter analysis revealed changes in fibre coherence in patients with Tourette syndrome within anterior parts of the corpus callosum. The severity of motor tics and premonitory urges had an impact on the integrity of tracts corresponding to cortico-cortical and cortico-subcortical connections. Our results provide empirical support for a patho-aetiological model of Tourette syndrome based on developmental abnormalities, with perturbation of compensatory systems marking persistence of symptoms into adulthood. We interpret the symptom severity related grey matter volume increase in distinct functional brain areas as evidence of ongoing structural plasticity. The convergence of evidence from volume and water diffusivity imaging strengthens the validity of our findings and attests to the value of a novel multimodal combination of volume and cortical thickness estimations that provides unique and complementary information by exploiting their differential sensitivity to structural change.

Adolescent survivors of childhood cancer: are they vulnerable for psychological distress?

OBJECTIVES: We aimed to (i) evaluate psychological distress in adolescent survivors of childhood cancer and compare them to siblings and a norm population; (ii) compare the severity of distress of distressed survivors and siblings with that of psychotherapy patients; and (iii) determine risk factors for psychological distress in survivors. METHODS: We sent a questionnaire to all childhood cancer survivors aged <16 years when diagnosed, who had survived ≥ 5 years and were aged 16-19 years at the time of study. Our control groups were same-aged siblings, a norm population, and psychotherapy patients. Psychological distress was measured with the Brief Symptom Inventory-18 (BSI-18) assessing somatization, depression, anxiety, and a global severity index (GSI). Participants with a T-score ≥ 57 were defined as distressed. We used logistic regression to determine risk factors. RESULTS: We evaluated the BSI-18 in 407 survivors and 102 siblings. Fifty-two survivors (13%) and 11 siblings (11%) had scores above the distress threshold (T ≥ 57). Distressed survivors scored significantly higher in somatization (p=0.027) and GSI (p=0.016) than distressed siblings, and also scored higher in somatization (p ≤ 0.001) and anxiety (p=0.002) than psychotherapy patients. In the multivariable regression, psychological distress was associated with female sex, self-reported late effects, and low perceived parental support. CONCLUSIONS: The majority of survivors did not report psychological distress. However, the severity of distress of distressed survivors exceeded that of distressed siblings and psychotherapy patients. Systematic psychological follow-up can help to identify survivors at risk and support them during the challenging period of adolescence.

Historia morbi atrocis--deux nouveaux cas de ruptures spontanées de l'oesophage (syndrome de Boerhaave) [Historia morbi atrocis--2 new cases of spontaneous rupture of the esophagus (Boerhaave syndrome)].]

We report the case of two patients hospitalized within a few weeks of each other and both presenting with spontaneous rupture of the esophagus whose evolution proved fatal. We take the opportunity of drawing attention to this rare and challenging disease, which is often diagnosed too late.

Congenital heart disease affects local gyrification in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2DS) is a common genetic condition associated with cognitive and learning impairments. In this study, we applied a three-dimensional method for quantifying gyrification at thousands of points over the cortical surface to imaging data from 44 children, adolescents, and young adults with 22q11.2DS (17 males, 27 females; mean age 17y 2mo [SD 9y 1mo], range 6-37y), and 53 healthy participants (21 males, 32 females; mean age 15y 4mo [SD 8y 6mo]; range 6-40y). Several clusters of reduced gyrification were observed, further substantiating the pattern of cerebral alterations presented by children with the syndrome. Comparisons within 22q11.2DS demonstrated an effect of congenital heart disease (CHD) on cortical gyrification, with reduced gyrification at the parieto-temporo-occipital junction in patients with CHD, as compared with patients without CHD. Reductions in gyrification can resemble mild polymicrogyria, suggesting early abnormal neuronal proliferation or migration and providing support for an effect of hemodynamic factors on brain development in 22q11.2DS. The results also shed light on the pathophysiology of acquired brain injury in other populations with CHD.

Nemaline myopathy revealed by respiratory failure in adults

Most forms of myopathy may involve the respiratory muscles and progress to respiratory failure. However, the diagnosis of myopathy is seldom considered in an adult patient with no history of muscle disease and presenting with respiratory failure. Nemaline myopathy (NM) is a rare disorder characterized by symmetrical diffuse muscle weakness and rod-like nemaline bodies in muscle fibers. Respiratory muscle involvement is a major determinant of mortality in congenital NM, but is rare in late onset NM. Here, we report that acute or chronic respiratory failure may be caused by NM in subjects with no known history of muscle disease. Adult-onset NM was diagnosed in a 67-year-old woman with chronic respiratory insufficiency. Late onset childhood NM was revealed by respiratory failure in twin sisters aged 31. The diagnosis was established by muscle biopsy and electron microscopy (and mutations in the nebulin gene in the two sisters). Long-term clinical improvement was obtained with non-invasive ventilation (NIV) in the three patients. In conclusion, respiratory failure in an adult patient with no known history may correspond to NM with diaphragm involvement. Long-term outcome may be favorable with NIV.