The cytological diagnosis of a 'benign thyroid lesion': is it a real safe diagnosis for the patient?

OBJECTIVE: In fine needle aspiration cytology (FNAC), the category of benign thyroid lesions (BTL), which constitutes 65-70% of all thyroid FNAC, and can be correctly diagnosed by morphology alone, is an important entity. A diagnosis of BTL denotes a lesion managed with follow-up unless found in conjunction with compressive symptoms. Although this diagnosis can be quite simple, there are cases in which the scant cellular or colloid component may pose diagnostic issues. Herein, we describe the experiences of evaluating BTL at two large academic institutions. We evaluated the clinical importance of a correct diagnosis of BTL to define the exact inherent risk of a false-negative result (FNR). METHODS: From January 2008 through to June 2013, 506 (3.6%) out of 15 850 patients with BTL underwent surgery. All nodules were sampled under sonographic guidance (US) and processed either with liquid-based cytology (LBC), Diff-Quik® smears or alcohol-Papanicolaou staining methods. RESULTS: The histological follow-up of 506 BTL series included 493 benign and 13 malignant lesions. The latter group included four follicular carcinomas (FC), two classic variants of papillary thyroid carcinoma (PTC), one macrofollicular PTC and six follicular variants of PTC (FVPC). The malignancy rate for the BTL category was 2.5%. CONCLUSIONS: When diagnosed by expert cytopathologists, BTL represents a robust diagnosis and might reduce the number of FNR. Additional diagnostic experience and a large case series could enable cytopathologists to recognise all the morphological entities of BTL. An important additional aid is the extensive sampling of the lesions to reduce issues related to a low cellularity.

The impact of a register on the management of neonatal cooling in Switzerland.

BACKGROUND: Therapeutic hypothermia following hypoxic ischaemic encephalopathy in term infants was introduced into Switzerland in 2005. Initial documentation of perinatal and resuscitation details was poor and neuromonitoring insufficient. In 2011, a National Asphyxia and Cooling Register was introduced. AIMS: To compare management of cooled infants before and after introduction of the register concerning documentation, neuromonitoring, cooling methods and evaluation of temperature variability between cooling methods. STUDY DESIGN: Data of cooled infants before the register was in place (first time period: 2005-2010) and afterwards (second time period: 2011-2012) was collected with a case report form. RESULTS: 150 infants were cooled during the first time period and 97 during the second time period. Most infants were cooled passively or passively with gel packs during both time periods (82% in 2005-2010 vs 70% in 2011-2012), however more infants were cooled actively during the second time period (18% versus 30%). Overall there was a significant reduction in temperature variability (p < 0.001) comparing the two time periods. A significantly higher proportion of temperature measurements within target temperature range (72% versus 77%, p < 0.001), fewer temperature measurements above (24% versus 7%, p < 0.001) and more temperatures below target range (4% versus 16%, p < 0.001) were recorded during the second time period. Neuromonitoring improved after introduction of the cooling register. CONCLUSION: Management of infants with HIE improved since introducing the register. Temperature variability was reduced, more temperature measurements in the target range and fewer temperature measurements above target range were observed. Neuromonitoring has improved, however imaging should be performed more often.

Therapeutic hypothermia in term infants after perinatal encephalopathy: the last 5 years in Switzerland.

BACKGROUND: Therapeutic hypothermia (TH) following perinatal asphyxial encephalopathy in term infants improves mortality and neurodevelopmental outcome. In Europe, most neonatal units perform active cooling whereas in Switzerland passive cooling is predominantly used. AIMS: (i) To determine how many infants were cooled within the last 5years in Switzerland, (ii) to assess the cooling methods, (iii) to evaluate the variation of temperature of different cooling methods, and (iv) to evaluate the use of neuromonitoring. STUDY DESIGN: Retrospective cohort study. PATIENTS: Notes of all cooled term infants between March 2005 and December 2010 in 9 perinatal and two paediatric intensive care centres were retrospectively reviewed. Active cooling was compared to passive cooling alone and to passive cooling in combination with gel packs. RESULTS: 150 infants were cooled. Twenty-seven (18.2%) were cooled actively, 34 (23%) passively and 87 (58.8%) passively in combination with gel packs. Variation of temperature was significantly different between the three methods. Passive cooling had a significant higher variation of temperature (SD of 0.89) than both passive cooling in combination with gel packs (SD of 0.79) and active cooling (SD of 0.76). aEEG before TH was obtained in 35.8% of the infants and 86.5% had full EEG. One cUS was performed in 95.3% and MRI in 62.2% of the infants. CONCLUSION: Target temperature can be achieved with all three cooling methods. Passive cooling has the highest variation of temperature. Neuromonitoring should be improved in Swiss neonatal and paediatric intensive care units. Our results stress the importance of national registries.

Abnormal interhemispheric connectivity in neonates with D-transposition of the great arteries undergoing cardiopulmonary bypass surgery.

BACKGROUND AND PURPOSE: Neonates with severe CHD require CPB within the first days of life. White matter injury can occur before surgery, and this may impair the long-term neurodevelopmental and psychosocial outcome. The purpose of this study was to assess the microstructural development of the CC in infants with CHD before and after CPB for transposition of the great arteries. MATERIALS AND METHODS: Fifteen patients with CHD and 11 age-matched HC were recruited. We separately quantified the parallel (E1) and perpendicular (E23) diffusions, the ADC, and FA of the genu of the CC and splenium of the CC before and after surgery. RESULTS: In presurgical measures of the genu of the CC, higher E23 (P = .018), higher ADC (P = .026), and lower FA (P = .033) values were measured compared with those in HC. In the postsurgery scans, the genu of the CC had higher E23 (P = .013), higher ADC (P = .012), and lower FA (P = .033) values compared with those in HC. There was no significant difference in any DTI indices between the pre- and postsurgical groups. CONCLUSIONS: We report abnormal microstructural development in the genu of the CC of infants with d-TGA before and after CPB. High E23, high ADC, and low FA values in the genu of the CC may be explained by abnormal axonal pruning, thinner myelin sheaths, smaller axonal diameters, or more oligodendrocytes. It appears that the genu of the CC is more vulnerable than the splenium of the CC in patients with CHD and may serve as a biomarker to identify infants at highest risk for adverse neurodevelopmental outcome.

In-line filter included into the syringe infusion pump assembly reduces flow irregularities.

PURPOSE: To evaluate whether an in-line filter inserted in the syringe pump infusion line assembly influences start-up times and flow irregularities during vertical pump displacement at low infusion rates. METHODS: Fluid delivery after syringe pump start-up and after vertical displacement of the syringe pump by -50 cm was determined gravimetrically at flow rates of 0.5, 1.0 and 2.0 ml h(-1). Measurements were repeated for each flow rate four times with two different syringe pumps with and without an in-line filter incorporated. Data are shown as median and range. RESULTS: Start-up times were reduced by an in-line filter at 0.5 ml h(-1) flow rate from 355.5 s (0-660) to 115 s (0-320), whereas the effect was attenuated at higher flow rates. Pooling of fluid into the infusion system after lowering the infusion syringe pump was halved in all flow rates tested. Amount of infusion bolus after elevating the syringe pump by 50 cm was not affected by an in-line filter. CONCLUSION: In the evaluated model in-line filters help to reduce flow irregularities and delay in drug delivery of syringe pumps at low flow rates and represent an option to optimize continuous administration of highly concentrated short-acting drugs at very small infusion rates.

Hypothermia for perinatal asphyxial encephalopathy.

BACKGROUND: Perinatal asphyxial encephalopathy occurs in 1 per 1000 live births and is associated with high mortality and morbidity. Therapeutic hypothermia increases intact survival and improves neurodevelopmental outcome in survivors. AIMS: To evaluate (i) the opinion and practice of therapeutic hypothermia as a therapy for moderate to severe perinatal asphyxial encephalopathy amongst Swiss neonatologists and paediatric intensive care specialists, (ii) the current clinical management of infants with perinatal asphyxial encephalopathy and (iii) the need for a national perinatal asphyxia and therapeutic hypothermia registry. METHODS: Two web-based questionnaires were sent to 18 senior staff physicians within the Swiss Neonatal Network. RESULTS: Therapeutic hypothermia was considered effective by all responders, however only 11 of 18 units provided therapeutic hypothermia. Cooling was initiated during transfer and performed passively in 82% of centres with a target rectal temperature of 33-34 °C. Most units ventilated infants with perinatal asphyxial encephalopathy if clinically indicated and 73% of responders gave analgesia routinely to cooled infants. Neuromonitoring included continuous amplitude integrated EEG (aEEG) and EEG. Neuroimaging included cranial ultrasound (cUS), magnetic resonance imaging (MRI) and computed tomography (CT). Sixty-seven percent of units treating infants with perinatal asphyxial encephalopathy performed MRI routinely. All heads of departments questioned indicated that a "Swiss National Asphyxia and Cooling Registry" is needed. CONCLUSIONS: In Switzerland, access to therapeutic hypothermia is widespread and Swiss neonatologists believe that therapeutic hypothermia for perinatal asphyxia is effective. National cooling protocols are needed for the management of infants with perinatal asphyxial encephalopathy in order to ensure safe cooling, appropriate monitoring, imaging and follow-up assessment. A national registry is needed to collect data on diagnosis, treatment, adverse events and outcome.

Involvement of parents in critical incidents in a neonatal-paediatric intensive care unit.

BACKGROUND: With more liberal visiting hours in paediatric intensive care practice, parents' presence at the bedside has increased. Parents may thus become involved in critical incidents as contributors or detectors of critical incidents or they may be affected by critical incidents. METHODS: Voluntary, anonymous, non-punitive critical incident reporting system. Parents' involvement in critical incidents has been evaluated retrospectively (January 2002 to August 2007). The reports were analysed regarding involvement of parents, age of child, unit (paediatric intensive care or intermediate neonatal nursery), critical incident severity, critical incident category, actual or potential harm to patient and/or parent (minor, moderate, major), delay between the critical incident and its detection, and implemented system changes. RESULTS: Overall, 2494 critical incidents have been reported. There were 101 critical incidents with parental involvement: parents as contributors to critical incident (18; 0.7%), parents discovering a critical incident (11; 0.4%), parents affected by critical incident (72; 2.9%). The most vulnerable categories regarding contribution and detection were drugs, line/drain disconnection, trauma and hygiene. Ten critical incidents precipitated by parents were of moderate severity and seven of potential major severity (six line/drain disconnections). The majority of the events (six) detected by parents were of potential moderate severity and four were of major severity. CONCLUSION: Because of their presence at the bedside, parents in the paediatric intensive care unit are inevitably involved in safety issues. It is not the parents' duty to guarantee the safety for their children, but parents should be encouraged to report anything that worries them. Only an established safety culture allows parents to articulate their concerns.

[Clinical evaluation of a pressure release valve for paediatric cuffed tracheal tubes]. / Klinische Evaluation eines Uberdruckventils für Kindertuben mit Cuff.

OBJECTIVE: The safe use of cuffed tracheal tubes for children necessitates a cuff pressure limitation at 20-25 cmH2O. The aim of the study was to evaluate the reliability and benefit of a new cuff pressure release valve (opening pressure 20 cmH2O) for children intubated with a cuffed tracheal tube. METHODS: In a prospective, observational trial cuff pressure was recorded in paediatric and adolescent patients intubated with a cuffed tracheal tube during sevoflurane/nitrous oxide anaesthesia. The cuff pressure release valve was interposed between the cuff manometer and the pilot balloon. In 25 patients measurements were started at the initial opening pressure (group A) and in a further 25 patients measurements were started at the minimal sealing cuff pressure (group B). RESULTS: A total of 50 patients, aged from 0.4 to 17.8 years (median 7.4 years) were enrolled in the study. The opening pressure measured (group A) was 19.7+/-0.8 cmH(2)O and the cuff sealing pressure (group B) was 11.7+/-2.9 cmH2O (range 6-16 cmH2O). Mean cuff pressure values in group A were 20.4+/-1.6 cmH2O and 16.5+/-3.3 cmH2O in group B. In one patient (group A) the cuff pressure exceeded 25 cmH2O and was manually decreased to 20 cmH2O. In total, 24 filling procedures (group A 14; group B 10) were required during 103.1 h of investigation because of cuff pressure drop and audible air leakage, mainly caused by cuff pressure increases and consequent releases during patient positioning. CONCLUSION: Our data demonstrate that the tested cuff pressure release valve was useful and reliable to limit cuff pressure in tracheal intubated children and adolescents within an acceptable pressure range.

Rapid pressure compensation by automated cuff pressure controllers worsens sealing in tracheal tubes.

BACKGROUND: Cyclic redistribution of air within the cuff during respiratory pressure changes creates a self-sealing mechanism which allows tracheal sealing, despite tracheal airway pressure being above baseline cuff inflation pressure. The aim of the present study was to investigate the effect of continuous automated cuff pressure regulation on tracheal sealing during cyclic respiratory pressure changes. METHODS: In vitro tracheal sealing was studied in four different high volume-low pressure (HVLP) tracheal tube cuffs size internal diameter 8.0 and 5.0 mm in combination with a conventional pressure manometer and two different automated pressure controllers (VBM Cuff Controller; Cuff Pressure Control Tracoe). Experiments were performed at 10, 15, 20, and 25 cm H(2)O cuff pressure during intermittent positive pressure ventilation with peak inspiratory pressures of 20 and 25 cm H(2)O. Air leakage was assessed spirometrically. Experiments were performed four times with each tube brand and size with two exemplars of each of the three cuff pressure controllers. RESULTS: Owing to immediate cuff pressure correction, tracheal sealing at cuff pressure below inspiratory pressure was reduced in most of the tracheal tube cuffs, except in those with reduced sealing characteristics when using the Pressure Control Tracoe compared with the conventional pressure manometer and the VBM Cuff Controller. Tracheal sealing with the Pressure Control Tracoe comparable with the other two devices was only achieved at cuff pressures of 20 and 25 cm H(2)O. CONCLUSIONS: Automated cuff pressure controllers with rapid pressure correction interfere with the self-sealing mechanism of high sealing HVLP tube cuffs and reduce their improved sealing characteristics.

Prenatal and neonatal MR imaging findings in oral-facial-digital syndrome type VI.

We report prenatal and neonatal neuroimaging findings in a case of oral-facial-digital syndrome type VI (OFDS VI). Prenatal MR imaging at 29 weeks' gestation showed hypoplastic cerebellar vermis and hemispheres, the molar tooth sign, and a hypothalamic hamartoma. Neonatal MR imaging confirmed these findings. The neonate developed breathing abnormalities and exhibited frontal bossing, multiple bucco-alveolar frenula, and postaxial hexadactyly of both hands. If the molar tooth sign and a hypothalamic hamartoma are present, prenatal diagnosis of OFDS VI is possible.

Measurement of tracheal wall pressure: a comparison of three different in vitro techniques.

We compared three different tracheal wall pressure measuring techniques in vitro. Using a high-volume, low-pressure, cuffed tracheal tube with an internal diameter of 7.5 mm and a model trachea, the pressure difference technique, the wall pressure membrane technique and the microchip sensor probe technique with and without lubrication were studied. Wall pressures were measured after sequential injections of 0.5 ml of air into the cuff at cuff pressures ranging from 0 to 50 mmHg. The coefficient of variance was largest for the microchip sensor probe technique with lubrication (29%) and without lubrication (214%), and was lower for the wall pressure membrane technique (22%) and the pressure difference technique (19%). The wall pressure membrane and pressure difference techniques provided comparable results. The microchip sensor probe technique considerably underestimated wall pressure. These findings have an impact on the interpretation of published data on tracheal or pharyngeal wall pressure using the microchip sensor probe technique.

An in vitro study of the compliance of paediatric tracheal tube cuffs and tracheal wall pressure.

Cuff volume-pressure curves and cuff pressure-tracheal wall pressure relationships were investigated in eight brands of currently available cuffed, paediatric tracheal tubes with internal diameters of 5.0 mm. Cuff volume-pressure curves were measured with the cuff unrestricted and with the cuff placed within a tracheal model with wall pressure measurements. With the tracheal tube cuffs, unrestricted cuff compliance at 20 cmH(2)O cuff pressure varied between 0.06 and 0.3 ml x cmH(2)O(-1). With the cuff restricted within the model trachea, all tracheal tube cuffs became considerably less compliant (0.01-0.09 ml x cmH(2)O(-1)). We found tracheal wall pressure was similar to the cuff pressure as long as the resulting cuff diameter was sufficiently large freely to drape the inner tracheal wall. We found that, regardless of whether a higher or lower compliant tube cuff was used, cuff hyperinflation uniformly resulted in potentially compromised tracheal mucosal blood flow; cuff pressure monitoring using cuff pressure limitation is therefore strongly recommended.

Outer diameter and shape of paediatric tracheal tube cuffs at higher inflation pressures.

Cuffed tracheal tubes are becoming increasingly popular in paediatric anaesthesia and intensive care medicine. To avoid cuff related complications and airway morbidity, a thorough understanding of cuff volume/pressure behaviour and management is required. In this study, the outer cuff diameter and form stability of the cuff at high cuff pressure were assessed in a series of different paediatric cuffed tracheal tubes with internal diameter of between 3.0 and 5.0 mm. The main findings were that small amounts of inflated air led to a rapid increase in cuff pressure and volume and that the outer cuff diameters increased to 2-2.5 times the age-corresponding internal tracheal diameter following inadvertent syringe inflation. Careful cuff inflation under cuff pressure monitoring and/or automatic cuff pressure release is recommended in paediatric tracheal tube cuffs to prevent airway damage caused by manual inflation, pilot balloon compression and nitrous oxide diffusion.

Nitrous oxide diffusion into the cuffs of disposable laryngeal mask airways.

The aim of this study was to investigate cuff pressure changes found in disposable size 3 laryngeal mask airways (LMAs) from different manufacturers during nitrous oxide exposure and to compare the results with the re-usable Classic LMA. In an in vitro experiment, laryngeal mask airway cuff pressures starting from a baseline pressure of 40 cm H(2)O were recorded using a pressure transducer for 60 min with the laryngeal mask airway cuff exposed to 66% N(2)O in oxygen. Cuff pressure increases within 5 min of nitrous oxide exposure were > 250% in the Classic LMA and were not significantly different from those found in the Marshall laryngeal mask airway. However, they were significantly greater than those in the Soft Seal, the Unique, the AMBU, and Intersurgical laryngeal mask airways, all of which demonstrated stable cuff pressure levels within the first 5 min. The cuff pressure increase following 60 min of nitrous oxide exposure was 13.0 +/- 1.1 and 14.6 +/- 0.7 cm H(2)O in the Intersurgical and Unique laryngeal mask airways, respectively, which was significantly lower than the cuff pressure increase in the Soft Seal and in the Ambu laryngeal mask airways (28.3 +/- 2.9 and 30.9 +/- 1.2 cm H(2)O, respectively). Unlike the re-usable Classic LMA and the disposable Marshall laryngeal mask airway, which have silicone cuffs, the disposable Ambu, Intersurgical, Portex Soft Seal and Unique laryngeal mask airways have cuffs constructed from PVC, which seems to be less susceptible to hyperinflation caused by nitrous oxide diffusion.

Overexpression and overactivation of Akt in thyroid carcinoma.

Enhanced activation of Akt occurs in Cowden's disease, an inherited syndrome of follicular thyroid, breast, colon, and skin tumors, via inactivation of its regulatory protein, PTEN. Whereas PTEN inactivation is uncommon in sporadic thyroid cancer, activation of growth factor pathways that signal through Akt is frequently identified. We hypothesized that Akt overactivation could be a common finding in sporadic thyroid cancer and might be important in thyroid cancer biology. We examined thyroid cancer cells lines and benign and malignant thyroid tissue for total Akt activation and isoform-specific Akt expression. In thyroid cancer cells, Akt 1, 2, and 3 proteins were expressed, total Akt was activated by insulin phosphatidylinositol 3'-kinase, and inhibition of phosphatidylinositol 3'-kinase reduced cell viability. In human thyroid tissue, increased levels of phosphorylated total Akt were identified in follicular but not papillary cancers compared with normal tissue. Levels of Akt 1 and 2 proteins and Akt 2 RNA were elevated only in the follicular cancers. In paired samples, Akt 1, 2, 3, and phospho-Akt levels were higher in five of six cancers, including three of three follicular cancers. These data suggest that Akt activation may play a role in the pathogenesis or progression of sporadic thyroid cancer.

Corticotropin- and thyrotropin-secreting pituitary microadenomas: detection by dynamic magnetic resonance imaging.

Hormone-secreting pituitary microadenomas are often not visible on magnetic resonance imaging (MRI). Diagnosis requires confirmatory endocrine test results and often an invasive procedure, inferior petrosal sinus sampling (IPSS). Improved pituitary imaging may eliminate the need for IPSS in some patients, as shown in the 2 women in this report. The first patient with hirsutism, weight gain, and hypertension had intermittent elevations of urinary free cortisol, abnormal results on a low-dose dexamethasone suppression test, and positive results on a dexamethasone-suppressed ovine corticotropin-releasing hormone test (corticotropin, increase of 122%; cortisol, increase of 118%). Gadolinium-enhanced MRI showed no focal lesion, but dynamic MRI (sequential images beginning immediately after contrast injection) revealed a right-sided 5-mm microadenoma, confirmed by transsphenoidal surgery. The second patient had a goiter, anxiety, increased free thyroxine and triiodothyronine levels, and a normal thyrotropin value with no response to thyrotropin-releasing hormone. Magnetic resonance imaging showed no lesion, but dynamic MRI detected an 8-mm microadenoma. Although about 8% to 10% of healthy persons have incidental pituitary lesions that are 3 mm or larger on MRI, identification of a distinct lesion and positive results on a dexamethasone-suppressed ovine corticotropin-releasing hormone test should decrease the probability of a false-positive result on an imaging study. We recommend that dynamic MRI be performed in any patient with a suspected microadenoma, before IPSS is performed.