Surveillance-embedded genomic outbreak resolution of methicillin-susceptible Staphylococcus aureus in a neonatal intensive care unit.

We observed an increase in methicillin-susceptible Staphylococcus aureus (MSSA) infections at a Dutch neonatal intensive care unit. Weekly neonatal MSSA carriage surveillance and cross-sectional screenings of health care workers (HCWs) were available for outbreak tracing. Traditional clustering of MSSA isolates by spa typing and Multiple-Locus Variable number tandem repeat Analysis (MLVA) suggested that nosocomial transmission had contributed to the infections. We investigated whether whole-genome sequencing (WGS) of MSSA surveillance would provide additional evidence for transmission. MSSA isolates from neonatal infections, carriage surveillance, and HCWs were subjected to WGS and bioinformatic analysis for identification and localization of high-quality single nucleotide polymorphisms, and in-depth analysis of subsets of isolates. By measuring the genetic diversity in background surveillance, we defined transmission-level relatedness and identified isolates that had been unjustly assigned to clusters based on MLVA, while spa typing was concordant but of insufficient resolution. Detailing particular subsets of isolates provided evidence that HCWs were involved in multiple outbreaks, yet it alleviated concerns about one particular HCW. The improved resolution and accuracy of genomic outbreak analyses substantially altered the view on outbreaks, along with apposite measures. Therefore, inclusion of the circulating background population has the potential to overcome current issues in genomic outbreak inference.

Maternal respiratory distress and successful reversal with sugammadex during intrauterine transfusion with fetal paralysis.

A 70 kg, 34-year-old woman at 29 weeks-of-gestation required intrauterine transfusion for Rh (D) alloimmunization. In the ambulatory treatment clinic, 19 mg of rocuronium was administered intramuscularly in split doses into the fetal buttock. The fetus moved and inadvertent maternal neuromuscular blockade occurred, leading to respiratory distress. The patient was transferred to the operating room where she had poor muscle tone, dyspnea and dysphonia. Sugammadex 100 mg was administered intravenously and complete resolution of neuromuscular blockade was demonstrated using a Neuromuscular Transmission™ monitor. When neuromuscular blocking agents are administered in ambulatory settings, management protocols, reversal agents, and skilled assistance should be immediately available for managing potentially life-threatening complications.

Does selective pleural irradiation of malignant pleural mesothelioma allow radiation dose escalation? : A planning study.

BACKGROUND: After lung-sparing radiotherapy for malignant pleural mesothelioma (MPM), local failure at sites of previous gross disease represents the dominant form of failure. Our aim is to investigate if selective irradiation of the gross pleural disease only can allow dose escalation. MATERIALS AND METHODS: In all, 12 consecutive stage I-IV MPM patients (6 left-sided and 6 right-sided) were retrospectively identified and included. A magnetic resonance imaging-based pleural gross tumor volume (GTV) was contoured. Two sets of planning target volumes (PTV) were generated for each patient: (1) a "selective" PTV (S-PTV), originating from a 5-mm isotropic expansion from the GTV and (2) an "elective" PTV (E-PTV), originating from a 5-mm isotropic expansion from the whole ipsilateral pleural space. Two sets of volumetric modulated arc therapy (VMAT) treatment plans were generated: a "selective" pleural irradiation plan (SPI plan) and an "elective" pleural irradiation plan (EPI plan, planned with a simultaneous integrated boost technique [SIB]). RESULTS: In the SPI plans, the average median dose to the S­PTV was 53.6 Gy (range 41-63.6 Gy). In 4 of 12 patients, it was possible to escalate the dose to the S­PTV to >58 Gy. In the EPI plans, the average median doses to the E­PTV and to the S­PTV were 48.6 Gy (range 38.5-58.7) and 49 Gy (range 38.6-59.5 Gy), respectively. No significant dose escalation was achievable. CONCLUSION: The omission of the elective irradiation of the whole ipsilateral pleural space allowed dose escalation from 49 Gy to more than 58 Gy in 4 of 12 chemonaive MPM patients. This strategy may form the basis for nonsurgical radical combined modality treatment of MPM.

The inner and outer of our thorax: silicone breast implants and pulmonary alveolar proteinosis.

Pulmonary alveolar (phospholipo)proteinosis (PAP) is a rare lung disease, predominantly autoimmune in nature. This case report describes a patient with insidious dyspnoea since 5 years and a milky appearance of her bronchoalveolar fluid, leading to the diagnosis of PAP. The onset of symptoms coincided with an exchange of her silicone breast implants. Giant cell reaction in axillary adenopathies pointed towards silicone leakage. Adjuvants, such as silicone, might boost pre-existing antigen reactions of the immune system, potentially leading to autoimmune phenomena.

Invasive staging of the mediastinum.

Staging of patients with lung cancer provides accurate information on the extent of disease and guides the choice of treatment. Non-invasive imaging techniques are safe, however these imaging techniques have limited accuracy in detection of mediastinal lymph node metastases. The American College of Chest Physicians guidelines for lung cancer staging recommend that patients with abnormal lymph nodes on CT or PET, or centrally located tumors without mediastinal LNs, should undergo invasive staging. Mediastinal nodal sampling has traditionally been performed by cervical mediastinoscopy. However, with the development of endoscopic needle aspiration techniques such as endobronchial ultrasound (EBUS) to guide transbronchial needle aspiration (TBNA) and endoscopic ultrasound (EUS), the diagnostic algorithm for lung cancer is changing.

Permanent pacemakers in pregnancy.

Advances in cardiology and cardiovascular surgery have increased the use of permanent pacemakers in young adults such that there are more women with pacemakers becoming pregnant. This case report describes the pregnancy and delivery of a young woman with a demand pacemaker and reviews the principles of management of cardiac pacemakers in pregnancy. As part of the multidisciplinary team including cardiology, anesthesia, nursing and caring for these patients, it is important that obstetricians be informed and follow the principles of management of cardiac pacemakers in pregnancy to continue to achieve successful pregnancy outcomes.

The TERT-CLPTM1L locus for lung cancer predisposes to bronchial obstruction and emphysema.

Clinical studies suggest that bronchial obstruction and emphysema increase susceptibility to lung cancer. We assessed the possibility of a common genetic origin and investigated whether the lung cancer susceptibility locus on chromosome 5p15.33 increases the risk for bronchial obstruction and emphysema. Three variants in the 5p15.33 locus encompassing the TERT and CLPTM1L genes were genotyped in 777 heavy smokers and 212 lung cancer patients. Participants underwent pulmonary function tests and computed tomography of the chest, and completed questionnaires assessing smoking behaviour. The rs31489 C-allele correlated with reduced forced expiratory volume in 1 s (p=0.006). Homozygous carriers of the rs31489 C-allele exhibited increased susceptibility to bronchial obstruction (OR 1.82, 95% CI 1.24-2.69; p=0.002). A similar association was observed for diffusing capacity of the lung for carbon monoxide (p=0.004). Consistent with this, CC-carriers had an increased risk of emphysema (OR 2.04, 95% CI 1.41-2.94; p=1.73 × 10(-4)) and displayed greater alveolar destruction. Finally, CC-carriers also had an increased risk for lung cancer (OR 1.90, 95% CI 1.21-2.99; p=0.005), and were more susceptible to developing both lung cancer and bronchial obstruction than lung cancer alone (OR 2.11, 95% CI 1.04-4.26; p=0.038). The rs31489 variant on 5p15.33 is associated with bronchial obstruction, presence and severity of emphysema, and lung cancer.

Staging of lung cancer. Do we need a diagnostic CT of the brain after an integrated PET/CT for the detection of brain metastases?

Brain CT has been recommended in staging of patients with lung cancer because of its usefulness in the detection of metastases. Purpose of this study is to examine if a diagnostic brain CT (CT,) can be obviated when an integrated PET/CT (PET/CT) is available. 87 consecutive patients underwent a diagnostic brain CT and a whole-body PET/CT within a period of 3 weeks to stage a known primary tumour. CT examinations were evaluated by two experienced neuroradiologists on the detection of brain lesions (benign and malignant). The results of PET/CT and CT reading were compared and both readings were compared with the clinical results. Statistical analysis was done by measuring sensitivity, specificity, PPV, NPV and accuracy. The relative accuracies were compared by a McNemar (exact) test for correlated proportions. Considering the CT, as standard of reference, sensitivity, specificity, PPV, NPV and accuracy for the brain CT of PET/CT (CT2) and PET/CT were respectively 83%, 96%, 77%, 97%, 94% and 69%, 98%, 90%, 95%, 94%. Considering the clinical diagnosis as standard of reference these figures were for CT1, CT2 and PET/CT respectively 80%, 100%, 100%, 96%, 96% and 66%, 95%, 77%, 93%, 90% and 66%, 97%, 83%, 93%, 91%. There was no statistical difference between CT1 and CT2. The comparison of the additional CT in PET/CT with a diagnostic CT of the brain did not yield a statistical difference in the detection of brain lesions despite the inferior quality of the CT component of PET/CT. A diagnostic brain CT can be obviated when a PET/CT is available.

Integrated PET/CT and cancer imaging.

Integrated Positron Emission Tomography/Computed Tomography (PET/CT) is an imaging technique that was introduced in clinical practice in 1998. PET/CT is the combination of two different examination techniques in one machine: Computed Tomography (CT) giving anatomic information and Positron Emission Tomography (PET) giving metabolic information. PET/CT has two major advantages: CT can be used for attenuation correction and PET/CT improves diagnostic accuracy when compared to CT and PET alone.The quality of PET/CT images depends on different parameters such as CT dose, patient respiration, and the use of intravenous (i.v.) and per oral (PO) contrast. A rapidly expanding amount of literature demonstrates the additional value of PET/CT in the diagnosis, staging, prognosis, treatment planning, assessment of treatment response and diagnosis of recurrence of many tumor types. CT increases the sensitivity of the PET/CT examination, but the most beneficial effect of having the CT data is the increase of the specificity of the PET data. PET data also helps to specify CT information.The utility of PET/CT for tumor staging, which is one of the major imaging study indication, seems to be very high, and therefore PET/CT may become the scanner of the future. Till this moment there are no many published studies about the cost-effectiveness of PET/CT. The integration of PET/CT in clinical practice will result in higher equipment running costs, but these costs are likely not to be prohibitive to the diffusion of this combined technology.

Integrated PET/CT in the staging of nonsmall cell lung cancer: technical aspects and clinical integration.

Lung cancer is a common disease and is a leading cause of death in many countries. The management of lung cancer is directed by an optimal staging of the tumour. Integrated positron emission tomography (PET)/computed tomography (CT) is an anatomo-metabolic imaging modality that has recently been introduced to clinical practice and combines two different techniques: CT, which provides very detailed anatomic information; and PET, which provides metabolic information. One of the advantages of PET/CT is the improved image interpretation. This improvement can result in the detection of lesions initially not seen on CT or PET, a more precise location of lesions, a better characterisation of the lesion as benign or malignant and a better differentiation between tumour and surrounding structures. Initial studies demonstrate better results for PET/CT in the staging of lung cancer in comparison with PET alone, CT alone or visual correlation of PET and CT. The purpose of the present article is to discuss technical aspects of integrated PET/CT and to attempt to outline how to introduce integrated PET/CT in clinical and daily practice.

A novel model used to compare water-perfused and solid-state anorectal manometry.

BACKGROUND: Anal pressures are commonly measured using water-perfused and solid-state manometers. We constructed a dynamic model of the anus to compare the agreement and reproducibility of the two types of manometers. METHODS: The model system was constructed using a pig anorectum together with an inflatable bowel sphincter. The pig anorectum was mounted on a jig and the sphincter was inserted external to the internal sphincter. The sphincter pressure was adjusted over the range 20 to 185 mmHg. At each of 24 constant sphincter pressures, triplicate readings were carried out with both manometers. The first measurement by each method was used for the comparison. The replicate measurements were used to calculate measures of repeatability for each method. RESULTS: Measurements by the two manometers were highly correlated (r=0.97). Measurements by the solid state manometer were higher than the water-perfused manometer by 8.1+/-12.2 mmHg (mean+/-SD). Precision (coefficient of variation) for the solid-state manometer (2.8%) was better than for the water-perfused manometer (8.3%). CONCLUSIONS: The new model of the anal canal shows promise as a tool for assessing physiological interventions. The solid-state manometer has many advantages over the water-perfused manometer, providing more consistent measurements at clinically relevant pressures.

Evaluation of knowledge and anxiety level of patients visiting the colorectal pelvic floor clinic.

OBJECTIVE: Discussing defaecating disorders is difficult for patients and many view anal physiology investigations (ultrasound, manometry, electromyography and pudendal nerve studies) as distasteful. This pilot study sought to assess whether present information sheets supplied to patients and the visit to the colorectal Pelvic Floor Clinic itself influenced patients' knowledge and anxiety. PATIENTS AND METHODS: Thirty Pelvic Floor Clinic patients from Auckland City Hospital were included. Each patient filled in a questionnaire before and after the clinic. This included objective questions about their knowledge of the structure and function of the pelvic floor and satisfaction with and understanding of the information sheet. Both visual analogue scale (VAS) and multiple choice questions (MCQ) were used. Their subjective and objective knowledge were compared. Anxiety was assessed on a visual analogue anxiety scale (VAAS). Results were expressed as VAS scores or percentage correct and relationships were tested using Fisher's Exact test and paired T-test. RESULTS: Subjective knowledge increased in 93% of the patients. The doctor's explanation led to a greater increase in subjective knowledge than the information sheet (35/100 mm, P<0.001 and 10/100 mm, P=0.01, respectively). Subjective improvement in knowledge did not however, translate into an increase in objective knowledge (P=0.63). The information sheet was read by 87% of the patients. The information sheet had reduced anxiety only in 23% of the patients and increased in 10%. Anxiety levels were not significantly influenced by the information sheet, but reduced significantly by the clinic visit in 87% of patients (P<0.001). The mean anxiety level reduced from 44/100 to 12/100 after the clinic visit. CONCLUSION: Anxiety levels are high in those visiting the Pelvic Floor Clinic. It appears that it is the interaction with the doctor that has a profound influence on anxiety levels and subjective knowledge rather than written information.

The effects of stress on alcohol consumption: mild acute and sub-chronic stressors differentially affect apomorphine susceptible and unsusceptible rats.

The aim of this study was to investigate the effects of mild acute and mild sub-chronic challenges on alcohol intake and preference in the genetically selected ratlines of apomorphine susceptible (APO-SUS) and apomorphine unsusceptible (APO-UNSUS) animals. Animals from both lines were subjected to the 24 hr continuous alcohol vs. water paradigm under baseline conditions, after a single stressor and after multiple stressors. The intake of alcohol in ml was measured and converted to two values, namely intake in g/kg/24 hour of, and preference for, alcohol. This study shows that under baseline conditions the APO-UNSUS animals consume/prefer more alcohol than the APO-SUS animals. After an acute challenge the APO-SUS animals show a large increase in consumption, whereas the APO-UNSUS animals display only a small increase. Furthermore, sub-chronic challenges can further increase the consumption of the APO-UNSUS rat, but not that of the APO-SUS rat. The APO-SUS/ APO-UNSUS rats represent a good model to study the interaction between genetic factors and stress on directing alcohol consumption.

Quantitative analysis of ultrasonic B-mode images.

Various sources of variability, such as speckle noise, depth dependence and inhomogeneous intervening tissue, are involved in B-mode images, even when using the same ultrasonic equipment with fixed settings. The behavior of these sources of variability was investigated by texture analysis of images obtained from simulations and from a tissue-mimicking phantom, a normal adult liver and a pediatric renal (Wilms') tumor. First-order statistics (MEAN and SNR) and second-order statistics from the co-occurrence matrix (ENT and COR) were calculated. In a phantom, the SNR and ENT show a clear depth dependence. In biological tissue, the variability is mainly caused by the speckle noise and inhomogeneous intervening tissue. In addition, almost the entire range of the COR feature is present in images of liver and tumor. Furthermore, all the features calculated in windows of 1 cm2 exhibit an overlap among the different media. With the second-order features, it is possible to discriminate 85% reliable (average) between the normal, adult, liver and the pediatric renal tumor above a window size of 9 cm2. The SNR can not discriminate between these tissues. The maximum resolution of 9 cm2 reveals a serious limitation of parametric imaging. Finally, the features reproduce well in the case of follow-up of an abdominal tumor during chemotherapy.

Follow-up of Wilms' tumour during pre-operative chemotherapy by qualitative and quantitative sonography.

OBJECTIVES: Evaluation of textural changes in Wilms' tumour during chemotherapy by qualitative and quantitative ultrasonography. METHODS: Sonograms of Wilms' tumours during chemotherapy were retrospectively evaluated (N=33) and compared with histopathology. Textural changes were prospectively quantified (N=6) by mean echogenicity (MEAN) and coefficient of variation (CV) of grey levels. RESULTS: Interobserver agreement for volume measurements was strong and for follow-up of sonolucencies moderate. Chemotherapy caused significant volume reduction and two major patterns of change in sonolucencies were observed; either increase or no change. No relationship between sonolucencies and volume changes was present. Sonolucencies yielded an underestimation of necrosis (P<0.001). Trends in MEAN and CV differed between patients. CONCLUSIONS: Volume was the most objective sonographic tumour response parameter. Changes in sonolucencies may provide additional information on tumour response. However, sonolucencies are not an accurate measure of total tumour necrosis. It was not possible to differentiate Wilms' tumour chemotherapy responders from non-responders by MEAN and CV.

Radiological aspects of Zenker's diverticulum.

In a retrospective study of 143 patients with Zenker's diverticulum followed for a period of 20 years, we classified the diverticula into 4 categories (A, B, C and D) using Brombart's scheme as a basis; the difference between the first two categories, however, was made on the basis of a morphological-dynamic criterion rather than a purely morphological one. Furthermore, a quantitative index was introduced to define the size of the diverticulum. In two cases we noted a substantial increase in volume with the transition from category C to D after more than 3 years, but we were unable to demonstrate an evolution from category A to B, nor from B to C. Our study confirms, on a large scale, the presence of three possible pathogenetic mechanisms, as proposed earlier in the literature: decreased relaxation of the upper esophageal sphincter as the most frequent factor in all categories except category A, and delayed opening or early closing of this sphincter as less frequent factors. The good relaxation of the upper esophageal sphincter in our category A, the different sex ratio and the absence of evolution in this category suggest that category A does not necessarily evolve further.