Comparison of bronchoscopic and non-bronchoscopic techniques for diagnosis of ventilator associated pneumonia

Background:

The diagnosis of ventilator associated pneumonia (VAP) remains a challenge because the clinical signs and symptoms lack both sensitivity and specificity and the selection of microbiologic diagnostic procedure is still a matter of debate.

Aims and Objective:

To study the role of various bronchoscopic and non-bronchoscopic diagnostic techniques for diagnosis of VAP.

Settings and Design:

This prospective comparative study was conducted in a medical ICU of a tertiary care center.

Materials and Methods:

Twenty-five patients, clinically diagnosed with VAP, were evaluated by bronchoscopic and non-bronchoscopic procedures for diagnosis. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of various bronchoscopic and non-bronchoscopic techniques were calculated, taking clinical pulmonary infection score (CPIS) of ≥6 as reference standard.

Results:

Our study has shown that for the diagnosis of VAP, bronchoscopic brush had a sensitivity, specificity, PPV and NPV of 94.9% [confidence interval (CI): 70.6–99.7], 57.1% (CI: 13.4–86.1), 85% (CI: 61.1–96) and 80% (CI: 21.9–98.7), respectively. Bronchoscopic bronchoalveolar lavage (BAL) had a sensitivity, specificity, PPV and NPV of 77.8% (CI: 51.9–92.6), 71.8% (CI: 24.1–94), 87.3% (CI: 60.4–97.8) and 55.5% (CI: 17.4–82.6), respectively. Sensitivity, specificity, PPV and NPV for non–bronchoscopic BAL (NBAL) were 83.3% (CI: 57.7–95.6), 71.43% (CI: 24.1–94), 88.2% (CI: 62.3–97.4) and 62.5% (CI: 20.2–88.2), respectively. Endotracheal aspirate (ETA) yield was only 52% and showed poor concordance with BAL (κ-0.351; P-0.064) and NBAL (k-0.272; P-0.161). There was a good microbiologic concordance among different bronchoscopic and non-bronchoscopic distal airway sampling techniques.

Conclusion:

NBAL is an inexpensive, easy, and useful technique for microbiologic diagnosis of VAP. Our findings, if verified, might simplify the approach for the diagnosis of VAP.     

Palliative Radiation in Primary Squamous Cell Carcinoma of Thyroid: A Rare Case Report

Primary squamous cell carcinoma of the thyroid is an extremely rare neoplasm with aggressive behavior. Until date, only around 60 cases have been reported in the literature. Primary treatment of the patient is radical surgery. With optimum treatment survival is not more than 6 months in this aggressive malignancy. However in our patient surgery it was not possible because of unresectability of the mass due to encroachment of major vessels. Hence, we have delivered radiotherapy alone, with which effective palliation could be achieved and patient is leading a good quality-of-life for last 1 year.     

Multimodality language mapping in patients with left-hemispheric language dominance on Wada test

Objective

We determined the utility of electrocorticography (ECoG) and stimulation for detecting language-related sites in patients with left-hemispheric language-dominance on Wada test.

Methods

We studied 13 epileptic patients who underwent language mapping using event-related gamma-oscillations on ECoG and stimulation via subdural electrodes. Sites showing significant gamma-augmentation during an auditory-naming task were defined as language-related ECoG sites. Sites at which stimulation resulted in auditory perceptual changes, failure to verbalize a correct answer, or sensorimotor symptoms involving the mouth were defined as language-related stimulation sites. We determined how frequently these methods revealed language-related sites in the superior-temporal, inferior-frontal, dorsolateral-premotor, and inferior-Rolandic regions.

Results

Language-related sites in the superior-temporal and inferior-frontal gyri were detected by ECoG more frequently than stimulation (p < 0.05), while those in the dorsolateral-premotor and inferior-Rolandic regions were detected by both methods equally. Stimulation of language-related ECoG sites, compared to the others, more frequently elicited language symptoms (p < 0.00001). One patient developed dysphasia requiring in-patient speech therapy following resection of the dorsolateral-premotor and inferior-Rolandic regions containing language-related ECoG sites not otherwise detected by stimulation.

Conclusions

Language-related gamma-oscillations may serve as an alternative biomarker of underlying language function in patients with left-hemispheric language-dominance.

Significance

Measurement of language-related gamma-oscillations is warranted in presurgical evaluation of epileptic patients.     

Independent predictors of neuronal adaptation in human primary visual cortex measured with high-gamma activity

Neuronal adaptation is defined as a reduced neural response to a repeated stimulus and can be demonstrated by reduced augmentation of event-related gamma activity. Several studies reported that variance in the degree of gamma augmentation could be explained by pre-stimulus low-frequency oscillations. Here, we measured the spatio-temporal characteristics of visually-driven amplitude modulations in human primary visual cortex using intracranial electrocorticography. We determined if inter-stimulus intervals or pre-stimulus oscillations independently predicted local neuronal adaptation measured with amplitude changes of high-gamma activity at 80-150 Hz. Participants were given repetitive photic stimuli with a flash duration of 20 μs in each block; the inter-stimulus interval was set constant within each block but different (0.2, 0.5, 1.0 or 2.0 s) across blocks. Stimuli elicited augmentation of high-gamma activity in the occipital cortex at about 30 to 90 ms, and high-gamma augmentation was most prominent in the medial occipital region. High-gamma augmentation was subsequently followed by lingering beta augmentation at 20-30 Hz and high-gamma attenuation. Neuronal adaptation was demonstrated as a gradual reduction of high-gamma augmentation over trials. Multivariate analysis demonstrated that a larger number of prior stimuli, shorter inter-stimulus interval, and pre-stimulus high-gamma attenuation independently predicted a reduced high-gamma augmentation in a given trial, while pre-stimulus beta amplitude or delta phase had no significant predictive value. Association between pre-stimulus high-gamma attenuation and a reduced neural response suggests that high-gamma attenuation represents a refractory period. The local effects of pre-stimulus beta augmentation and delta phase on neuronal adaptation may be modest in primary visual cortex.     

Septic shock in chronic dialysis patients: clinical characteristics,antimicrobial therapy and mortality

Objectives

To describe the clinical characteristics and in-hospital mortality of chronic dialysis-dependent end-stage kidney disease patients with septic shock in comparison to septic shock patients not receiving chronic dialysis.

Methods

Using an international, multicenter database, we conducted a retrospective analysis of data collected from 10,414 patients admitted to the intensive care unit (ICU) with septic shock from 1989 to 2013, of which 800 (7.7 %) were chronic dialysis patients. Data on demographic characteristics, sites of infection, microbial pathogens, antimicrobial usage patterns, and in-hospital mortality were aggregated and compared for chronic dialysis and non-dialysis patients. Multivariate time-varying Cox models with and without propensity score matching were constructed to determine the association between dialysis and in-hospital death.

Results

Septic shock secondary to central venous catheter infection, peritonitis, ischemic bowel, and cellulitis was more frequent in chronic dialysis patients. The isolation of resistant organisms (10.7 vs. 7.1 %; p = 0.005) and delays in receiving antimicrobials (6.0 vs. 5.0 h) were more common in chronic dialysis patients than in non-dialysis patients. Delayed appropriate antimicrobial therapy was associated with an increased risk of death in chronic dialysis patients (p < 0.0001). In-hospital death occurred in 54.8 and 49.0 % of chronic dialysis and non-dialysis patients, respectively. After propensity score matching, there was no difference in overall survival between chronic dialysis and non-dialysis patients, but survival in chronic dialysis patients decreased over time compared to non-dialysis patients.

Conclusions

The demographic and clinical characteristics of chronic dialysis patients with septic shock differ from those of similar non-dialysis patients. However, there was no significant difference in mortality between the chronic dialysis and non-dialysis patients with septic shock enrolled in this analysis.

     

Cause-effect relation between hyperfibrinogenemia and vascular disease

Elevated plasma levels of fibrinogen are associated with the presence of cardiovascular disease, but it is controversial whether elevated fibrinogen causally imparts an increased risk, and as such is a true modifier of cardiovascular disease, or is merely associated with disease. By investigating a transgenic mouse model of hyperfibrinogenemia, we show that elevated plasma fibrinogen concentration (1) elicits augmented fibrin deposition in specific organs, (2) interacts with an independent modifier of hemostatic activity to regulate fibrin turnover/deposition, (3) exacerbates neointimal hyperplasia in an experimental model of stasis-induced vascular remodeling, yet (4) may suppress thrombin generation in response to a procoagulant challenge. These findings provide direct experimental evidence that hyperfibrinogenemia is more than a by-product of cardiovascular disease and may function independently or interactively to modulate the severity and/or progression of vascular disease.     

PDEF and PDEF-induced proteins as candidate tumor antigens for T cell and antibody-mediated immunotherapy of breast cancer

Novel breast tumor antigens are needed to develop T cell and antibody-based vaccine immunotherapy approach against breast cancer. To this purpose, we have previously shown that PDEF is frequently over expressed in human breast tumors and exhibits highly restricted expression in normal human tissues that is primarily limited to normal prostate. Moreover, PDEF expression correlates with poor overall survival for breast cancer patients. Additionally, Pse (prostate-specific Ets, mouse homologue of PDEF) is immunogenic in female mice and PDEF sequence contains HLA-A2 binding potentially immunogenic peptides. Together, these observations support PDEF as a novel candidate breast tumor antigen. Further, we have identified certain PDEF-induced proteins including CEACAM6, B7-H4, and S100A7 as additional candidate breast tumor antigens.