Exploration of chest wall perforator vascular anatomy on standard breast MRI: A potential aid to chest wall perforator flap planning.

Local chest wall perforator flaps (CWPFs) are a volume replacement technique permitting breast-conserving surgery in patients who otherwise may require a mastectomy. These flaps are based on one or more perforating arteries arising from the lateral chest wall that travel through the soft tissue and into the sub-dermal plexus to perfuse the flap. Examples include the lateral intercostal and lateral thoracic artery perforators (LICAP and LTAP, respectively). Cross-sectional imaging of perforating vessels is not routinely performed, and vessels are mapped pre- and peri-operatively using a hand-held acoustic doppler device. As many breast cancer patients undergo pre-operative MRI scanning for oncological purposes, we investigated the role of MRI in mapping the vascular anatomy to aid with the surgical planning of CWPFs. We collated data retrospectively on a cohort of breast cancer patients who underwent breast MRI as part of routine pre-operative imaging. Axial 3D high-resolution dynamic contrast-enhanced MRI sequences with multiplanar reconstructions were analysed by a consultant radiologist. The presence and calibre of lateral chest wall perforator vessels were assessed. Fifty patients were suitable for inclusion. A consistent pattern of lateral chest wall vasculature was observed. Forty-eight patients (96%) demonstrated a bilateral lateral thoracic artery (LTA) descending inferiorly along the chest wall with two-thirds of these communicating with perforating intercostal vessels. True independent LICAP vessels were identified in six patients. From our observations, lateral CWPFs are dependent on an intricate intercommunication between intercostal vessels and the LTA which in turn supply perforators to the lateral chest wall donor site.

Assessing causal treatment effect estimation when using large observational datasets.

BACKGROUND: Recently, there has been a heightened interest in developing and evaluating different methods for analysing observational data. This has been driven by the increased availability of large data resources such as Electronic Health Record (EHR) data alongside known limitations and changing characteristics of randomised controlled trials (RCTs). A wide range of methods are available for analysing observational data. However, various, sometimes strict, and often unverifiable assumptions must be made in order for the resulting effect estimates to have a causal interpretation. In this paper we will compare some common approaches to estimating treatment effects from observational data in order to highlight the importance of considering, and justifying, the relevant assumptions prior to conducting an observational analysis. METHODS: A simulation study was conducted based upon a small cohort of patients with chronic obstructive pulmonary disease. Two-stage least squares instrumental variables, propensity score, and linear regression models were compared under a range of different scenarios including different strengths of instrumental variable and unmeasured confounding. The effects of violating the assumptions of the instrumental variables analysis were also assessed. Sample sizes of up to 200,000 patients were considered. RESULTS: Two-stage least squares instrumental variable methods can yield unbiased treatment effect estimates in the presence of unmeasured confounding provided the sample size is sufficiently large. Adjusting for measured covariates in the analysis reduces the variability in the two-stage least squares estimates. In the simulation study, propensity score methods produced very similar results to linear regression for all scenarios. A weak instrument or strong unmeasured confounding led to an increase in uncertainty in the two-stage least squares instrumental variable effect estimates. A violation of the instrumental variable assumptions led to bias in the two-stage least squares effect estimates. Indeed, these were sometimes even more biased than those from a naïve linear regression model. CONCLUSIONS: Instrumental variable methods can perform better than naïve regression and propensity scores. However, the assumptions need to be carefully considered and justified prior to conducting an analysis or performance may be worse than if the problem of unmeasured confounding had been ignored altogether.

Completion of hand-written surgical consent forms is frequently suboptimal and could be improved by using electronically generated, procedure-specific forms.

INTRODUCTION: Completion of hand-written consent forms for surgical procedures may suffer from missing or inaccurate information, poor legibility and high variability. We audited the completion of hand-written consent forms and trialled a web-based application to generate modifiable, procedure-specific consent forms. METHODS: The investigation comprised two phases at separate UK hospitals. In phase one, the completion of individual responses in hand-written consent forms for a variety of procedures were prospectively audited. Responses were categorised into three domains (patient details, procedure details and patient sign-off) that were considered "failed" if a contained element was not correct and legible. Phase two was confined to a breast surgical unit where hand-written consent forms were assessed as for phase one and interrogated for missing complications by two independent experts. An electronic consent platform was introduced and electronically-produced consent forms assessed. RESULTS: In phase one, 99 hand-written consent forms were assessed and the domain failure rates were: patient details 10%; procedure details 30%; and patient sign-off 27%. Laparoscopic cholecystectomy was the most common procedure (7/99) but there was significant variability in the documentation of complications: 12 in total, a median of 6 and a range of 2-9. In phase two, 44% (27/61) of hand-written forms were missing essential complications. There were no domain failures amongst 29 electronically-produced consent forms and no variability in the documentation of potential complications. CONCLUSION: Completion of hand-written consent forms suffers from wide variation and is frequently suboptimal. Electronically-produced, procedure-specific consent forms can improve the quality and consistency of consent documentation.

Patients' understanding of medical terminology used in the breast clinic.

This study evaluated patients' understanding of common terms used by breast surgeons in order to identify words which may need to be defined and explained during a clinic consultation. 95 patients completed the survey. 87% defined 'Surgeon' correctly whereas 'Radiographer' and 'Radiologist' were correctly defined by only 19% and 28% respectively. 26% correctly defined 'Pathologist' and 43% 'Oncologist'. Two-thirds of patients correctly defined 'Benign' (66%) and 'Malignant' (65%). 'Mammogram' and 'Ultrasound' were correctly defined by 39% and 8% respectively. 21% of patients correctly defined 'Multi-Disciplinary Team Meeting'. 1 in 5 patients correctly defined 'Chemotherapy' (20%) and 'Radiotherapy' (19%). This study has identified that many of the medical terms used in a consultation are not understood by patients. Education must be incorporated as a routine part of the consultation to enhance the patient experience and ensure they can actively participate in making informed decisions about their care.

High-quality CMV-specific CD4+ memory is enriched in the lung allograft and is associated with mucosal viral control.

The maintenance of CMV-specific T cell memory in lung transplant recipients (LTRs) is critical for host defense and allograft durability, particularly in donor(+) /recipient(-) (D(+) R(-) ) individuals who demonstrate increased mortality. We studied CD4(+) and CD8(+) CMV-specific memory responses to phosphoprotein 65 (pp65) in a prospective cohort of 18 D(+) R(-) LTRs, from bronchoalveolar lavage (BAL)-obtained lung mononuclear cells (LMNC) and PBMC. Unexpectedly, pp65-specific CD4(+) and CD8(+) IFN-γ memory responses from LMNC were similar, in contrast to persistent CD8(+) predominance in PBMC. Unlike the pulmonary CD8(+) predominance during acute primary infection, compartmental equalization occurred in the CMV-specific CD8(+) memory pool during chronic infection, whereas CMV-specific CD4(+) memory was enriched in the bronchoalveolar space. Moreover, CMV-specific CD4(+) memory T cells with multifunctional production of IFN-γ, TNF-α, IL-2 and MIP-1ß were significantly increased in LMNCs, in contrast to similar intercompartmental CD8(+) memory function. Moreover, the absolute number of CMV-specific CD4(+) IFN-γ(+) memory cells in BAL was significantly increased in LTRs exhibiting viral control compared to those with CMV early antigen positivity. Collectively, these data demonstrate both preferential distribution and functional quality of CMV-specific CD4(+) memory in the lung allograft during chronic infection, and show an important association with CMV mucosal immunity and viral control.

CD154 blockade abrogates allospecific responses and enhances CD4(+) regulatory T-cells in mouse orthotopic lung transplant.

Acute cellular rejection (ACR) is a common and important clinical complication following lung transplantation. While there is a clinical need for the development of novel therapies to prevent ACR, the regulation of allospecific effector T-cells in this process remains incompletely understood. Using the MHC-mismatched mouse orthotopic lung transplant model, we investigated the short-term role of anti-CD154 mAb therapy alone on allograft pathology and alloimmune T-cell effector responses. Untreated C57BL/6 recipients of BALB/c left lung allografts had high-grade rejection and diminished CD4(+) : CD8(+) graft ratios, marked by predominantly CD8(+) >CD4(+) IFN-γ(+) allospecific effector responses at day 10, compared to isograft controls. Anti-CD154 mAb therapy strikingly abrogated both CD8(+) and CD4(+) alloeffector responses and significantly increased lung allograft CD4(+) : CD8(+) ratios. Examination of graft CD4(+) T-cells revealed significantly increased frequencies of CD4(+) CD25(+) Foxp3(+) regulatory T-cells in the lung allografts of anti-CD154-treated mice and was associated with significant attenuation of ACR compared to untreated controls. Together, these data show that CD154/CD40 costimulation blockade alone is sufficient to abrogate allospecific effector T-cell responses and significantly shifts the lung allograft toward an environment predominated by CD4(+) T regulatory cells in association with an attenuation of ACR.

Entry exclusion in the IncHI1 plasmid R27 is mediated by EexA and EexB.

Conjugative plasmids have evolved entry exclusion mechanisms to inhibit redundant DNA transfer from donor cells into recipients harboring isogenic or closely related plasmids. This exclusion phenomenon has been documented in the incompatibility H group (IncH) plasmid R27. A cosmid library representing the majority of the large (180kb) R27 plasmid was transformed into recipient cells and a conjugation assay identified that an operon located in the conjugative transfer region 2 (Tra2) of R27, the Z operon, mediated entry exclusion in the IncH plasmid. Reverse-transcriptase analysis revealed that the Z operon is comprised of four genes, 015, eexB, 017, and eexA. Sub-cloning of the individual genes located within the Z operon and subsequent screening for the entry exclusion phenotype determined that two genes, eexA and eexB, independently inhibit the entry of IncH-related plasmids. Bacterial fractionation studies predominantly localized the EexA protein to the cytoplasmic membrane, and the EexB protein to the outer membrane. Recipient cells expressing EexA and EexB were unable to exclude the entry of R27 plasmids harboring mutations within the IncH entry exclusion genes eexA and eexB. The IncH entry exclusion proteins EexA and EexB likely prevent redundant plasmid transfer by interaction with one another.

Ruptured thoracoabdominal aortic aneurysm in a renal transplant patient with Alport's syndrome.

Alport's syndrome is a rare genetic disorder of type IV basement membrane collagen synthesis that typically presents with nephropathy, deafness, and ocular abnormalities. To the best of our knowledge, this is the first report in the world's literature of ruptured thoracoabdominal aortic aneurysm in a young patient with Alport's syndrome and a renal transplant. Hypotheses on an association between collagen disease in Alport's syndrome and aortic aneurysms are discussed.

Electrophysiological subtypes of psychotic states.

OBJECTIVE: This research sought neurobiological features common to psychotic states displayed by patients with different clinical diagnoses. METHOD: Cluster analysis with quantitative electroencephalographic (QEEG) variables was used to subtype drug-naïve, non-medicated, and medicated schizophrenic, depressed and alcoholic patients with psychotic symptoms, from the USA and Germany. QEEG source localization brain images were computed for each cluster. RESULTS: Psychotic patients with schizophrenia, depression and alcoholism, and drug- naïve schizophrenic patients, were distributed among six clusters. QEEG images revealed one set of brain regions differentially upregulated in each cluster and another group of structures downregulated in the same way in every cluster. CONCLUSION: Subtypes previously found among 94 schizophrenic patients were replicated in a sample of 390 non-schizophrenic as well as schizophrenic psychotics, and displayed common neurobiological abnormalities. Collaborative longitudinal studies using these economical methods might improve differential understanding and treatment of patients based upon these features rather than clinical symptoms.

Bang-bang control of feeding: role of hypothalamic and satiety signals.

Rats, people, and many other omnivores eat in meals rather than continuously. We show by experimental test that eating in meals is regulated by a simple bang-bang control system, an idea foreshadowed by Le Magnen and many others, shown by us to account for a wide range of behavioral data, but never explicitly tested or tied to neurophysiological facts. The hypothesis is simply that the tendency to eat rises with time at a rate determined by satiety signals. When these signals fall below a set point, eating begins, in on-off fashion. The delayed sequelae of eating increment the satiety signals, which eventually turn eating off. Thus, under free conditions, the organism eats in bouts separated by noneating activities. We report an experiment with rats to test novel predictions about meal patterns that are not explained by existing homeostatic approaches. Access to food was systematically but unpredictably interrupted just as the animal tried to start a new meal. A simple bang-bang model fits the resulting meal-pattern data well, and its elements can be identified with neurophysiological processes. Hypothalamic inputs can provide the set point for longer-term regulation carried out by a comparator in the hindbrain. Delayed gustatory and gastrointestinal aftereffects of eating act via the nucleus of the solitary tract and other hindbrain regions as neural feedback governing short-term regulation. In this way, the model forges real links between a functioning feedback mechanism, neuro-hormonal data, and both short-term (meals) and long-term (eating-rate regulation) behavioral data.

Prediction of longitudinal cognitive decline in normal elderly with subjective complaints using electrophysiological imaging.

An extensive literature reports changes in quantitative electroencephalogram (QEEG) with aging and a relationship between magnitude of changes and degree of clinical deterioration in progressive dementia. Longitudinal studies have demonstrated QEEG differences between mild cognitively impaired (MCI) elderly who go on to decline and those who do not. This study focuses on normal elderly with subjective cognitive complaints to assess the utility of QEEG in predicting future decline within 7 years. Forty-four normal elderly received extensive clinical, neurocognitive and QEEG examinations at baseline. All study subjects (N = 44) had only subjective complaints but no objective evidence of cognitive deficit (evaluated using the Global Deterioration Scale [GDS] score, GDS stage = 2) at baseline and were re-evaluated during 7-9 year follow-up. Baseline QEEGs of Decliners differed significantly (p < 0.0001, by MANOVA) from Non-Decliners, characterized by increases in theta power, slowing of mean frequency, and changes in covariance among regions, especially on the right hemisphere. Using logistic regression, an R2 of 0.93 (p < 0.001) was obtained between baseline QEEG features and probability of future decline, with an overall predictive accuracy of 90%. These data indicate high sensitivity and specificity for baseline QEEG as a differential predictor of future cognitive state in normal, subjectively impaired elderly.

[Topographic electroencephalography: endotracheal intubation during anaesthesia with propofol/fentanyl]. / Topographie des Elektroenzephalogramms: Endotracheale Intubation unter Narkose mit Propofol und Fentanyl -- EEG-Mapping während Intubation unter Propofol-/Fentanyl-Narkose.

OBJECTIVE: We used quantitative analysis of the electroencephalogram (EEG) during routine clinical practice to assess the effect of tracheal intubation following induction of anesthesia with propofol and fentanyl. METHODS: The topographic EEG was recorded from eight bipolar electrode derivations in 25 patients. Z-scores relative to age expected normative data were computed for relative power in the delta, theta, alpha and beta frequency bands. Multivariate statistics (Hotellings' t-sqare) were used to evaluate changes in regional brain electrical activity. RESULTS: Tracheal intubation induced an increase in alpha and beta frequencies, while delta power was reduced (F-values: Delta: 7.68, p = 0.011; Alpha 31.93; p < 0.001; Beta 12.85, p = 0.001). The most pronounced regional effect was seen for the alpha frequency band with the largest increase in both fronto-temporal regions (F-value 33.89, p < 0.001). During clinical practice the patients received propofol 2.7 (+/- 1.2; minimum: 0.5, maximum 6.9) mg kg (- 1) and fentanyl 2 (+/- 1; minimum 1, maximum 4) microg kg (- 1). Vital parameters did not change during intubation. CONCLUSION: Individual titration of the dose of propofol and fentanyl as done during routine clinical practice is not sufficient to block the strong noxious stimulation of intubation. Tracheal intubation resulted in "classical" cortical arousal. It remains open whether this cortical wake-up phenomenon has a clinical impact.

The effects of interval duration on temporal tracking and alternation learning.

On cyclic-interval reinforcement schedules, animals typically show a postreinforcement pause that is a function of the immediately preceding time interval (temporal tracking). Animals, however, do not track single-alternation schedules-when two different intervals are presented in strict alternation on successive trials. In this experiment, pigeons were first trained with a cyclic schedule consisting of alternating blocks of 12 short intervals (5 s or 30 s) and 12 long intervals (180 s), followed by three different single-alternation interval schedules: (a) 30 s and 180 s, (b) 5 s and 180 s, and (c) 5 s and 30 s. Pigeons tracked both schedules with alternating blocks of 12 intervals. With the single-alternation schedules, when the short interval duration was 5 s, regardless of the duration of the longer interval, pigeons learned the alternation pattern, and their pause anticipated the upcoming interval. When the shorter interval was 30 s, even when the ratio of short to long intervals was kept at 6:1, pigeons did not initially show anticipatory pausing-a violation of the principle of timescale invariance.

Timing in choice experiments.

In Experiment 1, pigeons chose between variable- and fixed-interval schedules. The timer for 1 schedule was reset by a reinforcement on that schedule or on either schedule. In both cases, the pigeons timed reinforcement on each schedule from trial onset. The data further suggest that their behavior reflects 2 independent processes: 1 deciding when a response should be emitted and responsible for the timing of the overall activity, and the other determining what this response should be and responsible for the allocation of behavior between the 2 response keys. Results from Experiment 2, which studied choice between 2 fixed-interval schedules, support those 2 conclusions. These results have implications for the study of operant choice in general.

Decreased EEG synchronization in Alzheimer's disease and mild cognitive impairment.

The hypothesis of a functional disconnection of neuro-cognitive networks in patients with mild cognitive impairment (MCI) and Alzheimer Dementia was investigated using baseline resting EEG data. EEG databases from New York (264 subjects) and Stockholm (155 subjects), including healthy controls and patients with varying degrees of cognitive decline or Alzheimer Dementia were analyzed using Global Field Synchronization (GFS), a novel measure of global EEG synchronization. GFS reflects the global amount of phase-locked activity at a given frequency by a single number; it is independent of the recording reference and of implicit source models. Patients showed decreased GFS values in Alpha, Beta, and Gamma frequency bands, and increased GFS values in the Delta band, confirming the hypothesized disconnection syndrome. The results are discussed within the framework of current knowledge about the functional significance of the affected frequency bands.

The conditions for temporal tracking under interval schedules of reinforcement.

On many cyclic-interval schedules, animals adjust their postreinforcement pause to follow the interval duration (temporal tracking). Six pigeons were trained on a series of square-wave (2-valued) interval schedules (e.g., 12 fixed-interval [FI] 60, 4 FI 180). Experiment 1 showed that pigeons track square-wave schedules, except those with a single long interval per cycle. Experiments 2 and 3 established that tracking and nontracking are learned and both can transfer from one cyclic schedule to another. Experiment 4 demonstrated that pigeons track a schedule with a single short interval per cycle, suggesting that a dual process--cuing and tracking--is necessary to explain behavior on these schedules. These findings suggest a potential explanation for earlier results that reported a failure to track square-wave schedules.

The Patient State Index as an indicator of the level of hypnosis under general anaesthesia.

BACKGROUND: This retrospective study describes the performance of the Patient State Index (PSI), under standard clinical practice conditions. The PSI is comprised of quantitative features of the EEG (QEEG) that display clear differences between hypnotic states, but consistency across anaesthetic agents within the state. METHODS: The PSI was constructed from a systematic investigation of a database containing QEEG extracted from the analyses of continuous 19 channel EEG recordings obtained in 176 surgical patients. Induction was accomplished with etomidate, propofol, or thiopental. Anaesthesia was maintained by isoflurane, desflurane, or sevoflurane, total i.v. anaesthesia using propofol, or nitrous oxide/narcotics. It was hypothesized that a multivariate algorithm based on such measures of brain state, would vary significantly with changes in hypnotic state. RESULTS: Highly significant differences were found between mean PSI values obtained during the different anaesthetic states selected for study. The relationship between level of awareness and PSI value at different stages of anaesthetic delivery was also evaluated. Regression analysis for prediction of arousal level using PSI was found to be highly significant for the combination of all anaesthetics, and for the individual anaesthetics. CONCLUSIONS: The PSI, based upon derived features of brain electrical activity in the anterior/posterior dimension, significantly co-varies with changes in state under general anaesthesia and can significantly predict the level of arousal in varying stages of anaesthetic delivery.

Changes in cortical electrical activity during induction of anaesthesia with thiopental/fentanyl and tracheal intubation: a quantitative electroencephalographic analysis.

BACKGROUND: There are regional differences in the effects of anaesthetics agents and perioperative stimuli on the EEG. We studied the topography of the EEG during induction of anaesthesia and intubation in patients receiving thiopental and fentanyl to document regional electrical brain activity. METHODS: EEG was recorded in 25 patients in the awake state, after pre-medication, during induction, at loss of consciousness and after intubation. Eight bipolar recordings were made and the relative power of the frequency bands delta, theta, alpha, and beta were used (after z-score transformation for age) to measure changes in regional EEG activity. RESULTS: Noxious stimulation during tracheal intubation partially reversed the slowing of the EEG caused by anaesthesia. During induction of anaesthesia alpha activity was most reduced in temporal and occipital regions. The most prominent EEG changes after intubation were an increase in alpha and a decrease in delta power (P<0.001). The largest changes were in the frontal and temporal leads for alpha and in the frontal and central leads for delta. Heart rate and arterial pressure remained constant during intubation. CONCLUSIONS: Changes in alpha and delta power were identified as the most sensitive EEG measures of regional changes in electrical brain activity during anaesthesia and noxious stimulation.